US6441163B1 - Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents - Google Patents

Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents Download PDF

Info

Publication number
US6441163B1
US6441163B1 US09/867,598 US86759801A US6441163B1 US 6441163 B1 US6441163 B1 US 6441163B1 US 86759801 A US86759801 A US 86759801A US 6441163 B1 US6441163 B1 US 6441163B1
Authority
US
United States
Prior art keywords
maytansinoid
ester
reactive
bears
maytansine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US09/867,598
Other languages
English (en)
Inventor
Ravi V. J. Chari
Wayne C. Widdison
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Immunogen Inc
Original Assignee
Immunogen Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25350107&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US6441163(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Immunogen Inc filed Critical Immunogen Inc
Priority to US09/867,598 priority Critical patent/US6441163B1/en
Assigned to IMMUNOGEN, INC. reassignment IMMUNOGEN, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CHARI, RAVI V.J., WIDDISON, WAYNE C.
Priority to CA2417858A priority patent/CA2417858C/fr
Priority to DK11003908.8T priority patent/DK2348024T3/en
Priority to ES11003908.8T priority patent/ES2551233T3/es
Priority to EP02720913.9A priority patent/EP1390370B1/fr
Priority to ES02720913.9T priority patent/ES2574640T3/es
Priority to PCT/US2002/003378 priority patent/WO2002098883A1/fr
Priority to PT110039088T priority patent/PT2348024E/pt
Priority to AU2002251880A priority patent/AU2002251880B2/en
Priority to EP11003908.8A priority patent/EP2348024B1/fr
Priority to DK02720913.9T priority patent/DK1390370T3/en
Priority to JP2003502004A priority patent/JP5190170B2/ja
Priority to PT02720913T priority patent/PT1390370E/pt
Priority to NZ523655A priority patent/NZ523655A/en
Priority to US10/161,651 priority patent/US7368565B2/en
Publication of US6441163B1 publication Critical patent/US6441163B1/en
Application granted granted Critical
Priority to HK04103250.5A priority patent/HK1060355A1/zh
Priority to HK11107839.7A priority patent/HK1149765A1/xx
Assigned to IMMUNOGEN, INC. reassignment IMMUNOGEN, INC. ADDRESS CHANGE Assignors: IMMUNOGEN, INC.
Priority to JP2010085225A priority patent/JP5271302B2/ja
Priority to CY20151100954T priority patent/CY1116855T1/el
Priority to CY20161100623T priority patent/CY1117729T1/el
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an improved method for preparing cytotoxic conjugates comprising maytansinoids and cell binding agents. These conjugates have therapeutic use as they are delivered to a specific cell population in a targeted fashion.
  • the present invention also relates to a method for preparing maytansinoids having a disulfide moiety that bears a reactive group which may be used in the preparation of cytotoxic conjugates.
  • the present invention further relates to novel maytansinoids.
  • Cytotoxic drugs such as methotrexate, daunorubicin, doxorubicin, vincristine, vinblastine, melphalan, mitomycin C, and chlorambucil have been conjugated to a variety of murine monoclonal antibodies.
  • the drug molecules were linked to the antibody molecules through an intermediary carrier molecule such as serum albumin (Garnett et al. Cancer Res. 46:2407-2412 (1986); Ohkawa et al. Cancer Immumol. Immunother. 23:81-86 (1986); Endo et al. Cancer Res. 47:1076-1080 (1980)), dextran (Hurwitz et al. Appl. Biochem. 2:25-35 (1980); Manabi et al.
  • One of the cleavable linkers that has been employed for the preparation of antibody-drug conjugates is an acid-labile linker based on cis-aconitic acid that takes advantage of the acidic environment of different intracellular compartments such as the endosomes encountered during receptor mediated endocytosis and the lysosomes.
  • Shen and Ryser introduced this method for the preparation of conjugates of daunorubicin with macromolecular carriers ( Biochem. Biophys. Res. Commun. 102:1048-1054 (1981)).
  • Yang and Reisfeld used the same technique to conjugate daunorubicin to an anti-melanoma antibody ( J. Natl. Canc. Inst. 80:1154-1159 (1988)).
  • Dillman et al. also used an acid-labile linker in a similar fashion to prepare conjugates of daunorubicin with an anti-T cell antibody ( Cancer Res. 48:6097-6102 (1988)).
  • Another major drawback with existing antibody-drug conjugates is their inability to deliver a sufficient concentration of drug to the target site because of the limited number of targeted antigens and the relatively moderate cytotoxicity of cancerostatic drugs like methotrexate, daunorubicin and vincristine.
  • cancerostatic drugs like methotrexate, daunorubicin and vincristine.
  • linkage of a large number of drug molecules either directly to the antibody or through a polymeric carrier molecule becomes necessary.
  • heavily modified antibodies often display impaired binding to the target antigen and fast in vivo clearance from the blood stream.
  • Maytansinoids are highly cytotoxic drugs. Maytansine was first isolated by Kupchan et al. from the east African shrub Maytenus serrata and shown to be 100 to 1000 fold more cytotoxic than conventional cancer chemotherapeutic agents like methotrexate, daunorubicin, and vincristine (U.S. Pat. No. 3,896,111). Subsequently, it was discovered that some microbes also produce maytansinoids, such as maytansinol and C-3 esters of maytansinol (U.S. Pat. No. 4,151,042). Synthetic C-3 esters of maytansinol and analogues of maytansinol have also been reported (Kupchan et al. J. Med.
  • Examples of analogues of maytansinol from which C-3 esters have been prepared include maytansinol with modifications on the aromatic ring (e.g. dechloro) or at the C-9, C-14 (e.g. hydroxylated methyl group), C-15, C-18, C-20 and C-4,5.
  • the naturally occurring and synthetic C-3 esters can be classified into two groups:
  • Esters of group (b) were found to be much more cytotoxic than esters of group (a).
  • Maytansine is a mitotic inhibitor. Treatment of L1210 cells in vivo with maytansine has been reported to result in 67% of the cells accumulating in mitosis. Untreated control cells were reported to demonstrate a mitotic index ranging from between 3.2 to 5.8% (Sieber et al. 43 Comparative Leukemia Research 1975, Bibl. Haemat. 495-500 (1976)). Experiments with sea urchin eggs and clam eggs have suggested that maytansine inhibits mitosis by interfering with the formation of microtubules through the inhibition of the polymerization of the microtubule protein, tubulin (Remillard et al. Science 189:1002-1005 (1975)).
  • maytansine has also been shown to be active. Tumor growth in the P388 lymphocytic leukemia system was shown to be inhibited over a 50- to 100-fold dosage range which suggested a high therapeutic index; also significant inhibitory activity could be demonstrated with the L1210 mouse leukemia system, the human Lewis lung carcinoma system and the human B-16 melanocarcinoma system (Kupchan, Ped. Proc. 33:2288-2295 (1974)).
  • a cell binding agent for example an antibody
  • a cross-linking reagent such as N-succinimidyl pyridyldithiopropionate (SPDP) to introduce dithiopyridyl groups into the antibody
  • SPDP N-succinimidyl pyridyldithiopropionate
  • a reactive maytansinoid having a thiol group such as DM 1
  • DM 1 a reactive maytansinoid having a thiol group
  • a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents is disclosed.
  • Maytansinoids having a disulfide moiety that bears a reactive group are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent.
  • This conjugation process minimizes the reaction time and processing time for the sensitive antibody protein molecules, and also minimizes the protein purification steps, thus improving the overall yield.
  • conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.
  • the present invention discloses novel methods for the synthesis of maytansinoids having a disulfide moiety that bears a reactive group.
  • Maytansinoids are organic molecules that are sensitive to aqueous conditions of low (pH 5 and lower) or high pH (pH 8 and higher) and have poor solubilities in aqueous solutions.
  • the novel method disclosed here overcomes these problems by converting maytansinoids to maytansinoids having a disulfide moiety that bears a reactive group, in organic solvents or mixtures of aqueous and organic solvents.
  • the resulting reactive maytansinoid derivatives have better solubilities in aqueous solutions and can be conjugated to cell binding agents in a single reaction step in aqueous buffers under mild conditions (pH 6-8).
  • An additional advantage is that all the maytansinoid intermediates in the process can be fully analyzed before they are conjugated. Synthesis of suitable maytansinoids having a disulfide moiety that bears a reactive group such as compounds 2 and 3 a discussed below, are described.
  • a method of producing other maytansinoid derivatives such as compounds 6 and 10 , that may be used in the production of maytansinoids having a disulfide moiety that bears a reactive group, such as compounds 2 and 3 a , is disclosed.
  • FIG. 1 shows the results of an experiment assaying the ability of huN 901 -maytansinoid conjugates prepared with 2 by the method of the present invention, followed by purification either by Sephacryl S 300 ( ⁇ ) or Sephadex G 25 ( ⁇ ) chromatography, and the unconjugated huN 901 antibody ( ⁇ ) to kill antigen positive cells.
  • FIG. 2 shows the synthesis pathway of maytansinoids having a disulfide moiety that bears a reactive group.
  • FIG. 3 shows an alternative synthesis pathway of maytansinoids having a disulfide moiety that bears a reactive group.
  • FIG. 4 shows the synthesis pathway of cytotoxic conjugates.
  • FIG. 5 shows an alternative pathway for the production of L-DM 1 -TPA (compound 6 ).
  • This invention discloses a one-step process for the synthesis of cytotoxic conjugates comprising maytansinoids and cell binding agents.
  • the invention also discloses a process for the synthesis of novel maytansinoids having a disulfide moiety that bears a reactive group, such as compounds 2 and 3 a .
  • this invention describes a process for the synthesis of novel maytansinoid derivatives, such as compounds 6 and 10 .
  • This invention further describes novel maytansinoid derivatives, such as compounds 6 and 10 , which are useful in the production of maytansinoids having a disulfide moiety that bears a reactive group.
  • This invention also further describes novel maytansinoids having a disulfide moiety that bears a reactive group, such as compounds 2 and 3 a , which are useful for the synthesis of novel cytotoxic conjugates.
  • the art reveals that it is extremely difficult to modify existing drugs without diminishing their cytotoxic potential.
  • the disclosed invention overcomes this problem by teaching a method of modifying maytansinoid molecules with reactive chemical moieties, especially maytansinoid molecules containing a disulfide moiety and a reactive group, which allows linkage to appropriate cell binding agents.
  • the disclosed novel maytansinoids having a disulfide moiety that bears a reactive group preserve, and in some cases even enhance, the cytotoxic potency of the naturally occurring maytansinoids.
  • the cytotoxic maytansinoid-cell binding agent conjugates permit the full measure of the cytotoxic action of the maytansinoid derivatives to be applied in a targeted fashion against unwanted cells only, thereby avoiding side effects due to damage to non-targeted healthy cells.
  • the invention provides useful agents, and novel methods for making the same, for the elimination of diseased or abnormal cells that are to be killed or lysed, such as tumor cells (particularly solid tumor cells), virus infected cells, microorganism infected cells, parasite infected cells, autoimmune cells (cells that produce autoantibodies), activated cells (those involved in graft rejection or graft vs. host disease), or any other type of diseased or abnormal cells, while exhibiting a minimum of side effects.
  • diseased or abnormal cells that are to be killed or lysed, such as tumor cells (particularly solid tumor cells), virus infected cells, microorganism infected cells, parasite infected cells, autoimmune cells (cells that produce autoantibodies), activate
  • this invention teaches a one-step method for the production of cytotoxic conjugates comprising maytansinoids and cell binding agents.
  • the invention further teaches a method for the synthesis of maytansinoid derivatives, and maytansinoids having a disulfide moiety that bears a reactive group that allows chemical linkage to a cell binding agent while keeping a high cytotoxicity either in bound form or in released form or in both states.
  • the invention discloses maytansinoid derivatives useful in the production of maytansinoids having a disulfide moiety that bears a reactive group, and maytansinoids having a disulfide moiety that bears a reactive group useful for the synthesis of novel cytotoxic conjugates.
  • the cytotoxic conjugate according to the present invention comprises one or more maytansinoids linked to a cell binding agent.
  • the maytansinoid In order to link the maytansinoid to a cell binding agent, the maytansinoid must first be modified.
  • Maytansinoids that can be used in the present invention to produce the reactive maytansinoid derivatives capable of being linked to a cell binding agent are well known in the art and can be isolated from natural sources according to known methods or prepared synthetically according to known methods.
  • Suitable maytansinoids include maytansinol and maytansinol analogues.
  • suitable maytansinol analogues include those having a modified aromatic ring and those having modifications at other positions.
  • Suitable analogues of maytansinol having a modified aromatic ring include:
  • C-9-SH (U.S. Pat. No. 4,424,219) (prepared by the reaction of maytansinol with H 2 S or P 2 S 5 );
  • the maytansinoid comprises a linking moiety.
  • the linking moiety contains a chemical bond that allows for the release of fully active maytansinoids at a particular site. Suitable chemical bonds are well known in the art and include disulfide bonds, acid labile bonds, photolabile bonds, peptidase labile bonds and esterase labile bonds. Preferred are disulfide bonds.
  • the linking moiety comprises a reactive chemical group.
  • the reactive chemical group can be covalently bound to the maytansinoid via a disulfide bond linking moiety.
  • Particularly preferred reactive chemical groups are N-succinimidyl esters and N-sulfosuccinimidyl esters.
  • Particularly preferred maytansinoids comprising a linking moiety that contains a reactive chemical group are C-3 esters of maytansinol and its analogs where the linking moiety contains a disulfide bond and the chemical reactive group comprises a N-succinimidyl or N-sulfosuccinimidyl ester.
  • maytansinoids can serve as the position to chemically link the linking moiety.
  • the C-3 position having a hydroxyl group, the C-14 position modified with hydroxymethyl, the C-15 position modified with hydroxy and the C-20 position having a hydroxy group are all expected to be useful.
  • the C-3 position is preferred and the C-3 position of maytansinol is especially preferred.
  • DM 1 thiol-containing maytansinoid
  • N 2′ -deacetyl-N 2′ -(3-mercapto-1-oxopropyl)-maytansine N 2′ -deacetyl-N 2′ -(3-mercapto-1-oxopropyl)-maytansine
  • Representational cytotoxic conjugates of the invention are antibody/maytansinoid, antibody fragment/maytansinoid, epidermal growth factor (EGF)/maytansinoid, melanocyte stimulating hormone (MSH)/maytansinoid, thyroid stimulating hormone (TSH)/maytansinoid, estrogen/maytansinoid, estrogen analogue/maytansinoid, androgen/maytansinoid, and androgen analogue/maytansinoid.
  • EGF epidermal growth factor
  • MSH melanocyte stimulating hormone
  • TSH thyroid stimulating hormone
  • the reactive group containing maytansinoid is reacted with a cell binding agent to produce cytotoxic conjugates.
  • conjugates may be purified by HPLC or by gel-filtration.
  • Scheme 1 More specifically, a solution of an antibody in aqueous buffer may be incubated with a molar excess of maytansinoids having a disulfide moiety that bears a reactive group.
  • the reaction mixture can be quenched by addition of excess amine (such as ethanolamine, taurine, etc.).
  • excess amine such as ethanolamine, taurine, etc.
  • the maytansinoid-antibody conjugate may then be purified by gel-filtration.
  • the number of maytansinoid molecules bound per antibody molecule can be determined by measuring spectrophotometrically the ratio of the absorbance at 252 nm and 280 nm. An average of 1-10 maytansinoid molecules/antibody molecule can be linked by this method.
  • Conjugates of cell binding agents with maytansinoid drugs of the invention can be evaluated for their ability to suppress proliferation of various unwanted cell lines in vitro.
  • cell lines such as the human epidermoid carcinoma line A-431, the human small cell lung cancer cell line SW2, the human breast tumor line SKBR3 and the Burkitt's lymphoma line Namalwa can easily be used for the assessment of cytotoxicity of these compounds.
  • Cells to be evaluated can be exposed to the compounds for 24 hours and the surviving fractions of cells measured in direct assays by known methods. IC 50 values can then be calculated from the results of the assays.
  • novel maytansinoids having a disulfide moiety that bears a reactive group disclosed in the present invention are those compounds represented by formula 11:
  • R 1 and R 2 are each independently H, CH 3 , C 2 H 5 , linear or branched higher alkyl,
  • n 1-5
  • X is a part of an active ester, and can be N-succinimidyl, N-sulfosuccinimidyl, N-phthalimidyl, N-sulfophthalimidyl, 2-nitrophenyl, 4-nitrophenyl, 2,4-dinitrophenyl, 3-sulfonyl-4-nitrophenyl, or 3-carboxy-4-nitrophenyl.
  • linear alkyls examples include propyl, butyl, pentyl and hexyl.
  • branched alkyls examples include isopropyl, isobutyl, sec.-butyl, tert.-butyl, isopentyl and 1-ethyl-propyl.
  • Preferred embodiments of formula 11 include those maytansinoids having a disulfide moiety that bears a reactive CO 2 —X ester, where X is N-succinimidyl or N-sulfosuccinimidyl. More preferred embodiments of formula 11 include those maytansinoids having a disulfide moiety that bears a reactive group where R 1 is H, R 2 is CH 3 , n is 2, and CO 2 —X is an active N-succinimidyl ester (compound 2 ) or CO 2 —X is an active N-sulfosuccinimidyl ester (compound 3 a ).
  • Novel maytansinoids having a disulfide moiety that bears a reactive group may be prepared by the following newly disclosed methods.
  • the maytansinoid having a disulfide moiety that bears a reactive N-succinimidyl ester (compound 2 ) may be prepared by the reaction of N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine (compound 6 ) with N-hydroxysuccinimide in a dry organic solvent in the presence of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.HCl (EDC.HCl) at ambient temperature for approximately 1-12 h.
  • EDC.HCl 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.HCl
  • reaction completion may be monitored with standard chemical techniques such as thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).
  • TLC thin layer chromatography
  • HPLC high performance liquid chromatography
  • the maytansinoid derivative having a disulfide moiety that bears a reactive N-succinimidyl ester (compound 2 ) may be purified using silica gel chromatography or HPLC.
  • Condensing agents other than EDC.HCl may also be employed for the reaction, such as N,N′-dicyclohexylcarbodiimide (DCC).
  • the maytansinoid having a disulfide moiety that bears a reactive N-sulfosuccinimidyl ester (compound 3 a ) may be prepared by the reaction of N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine (compound 6 ) with N-hydroxysulfosuccinimide sodium salt (1-2-fold molar excess over acid (6)) in a dry organic solvent (such as methylene chloride, dimethylformamide, tetrahydrofuran, dioxane, diethylether) in the presence of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.HCl (EDC.HCl) (1-2-fold molar excess over acid (6)).
  • a dry organic solvent such as methylene chloride, dimethylformamide, t
  • Completion of reaction may be monitored using standard chemical techniques such as TLC or HPLC.
  • the maytansinoid derivative having a disulfide moiety that bears a reactive N-sulfosuccinimidyl ester (compound 3 a ) may be purified by silica gel chromatography, or by HPLC, or by precipitation by addition of large volumes of ethyl acetate (similar to the general method of preparation of N-sulfosuccinimidyl esters as described by Staros, Biochemistry, 1982, 21:3950-3955).
  • Condensing agents other than EDC.HCl can be employed for the reaction.
  • Schemes 4a and 4b disclose novel methods for the production of a maytansinoid derivative from DM 1 ( 1 ).
  • This maytansinoid derivative 6 is formally termed N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine and represented by the formula:
  • Maytansinoid derivative 6 may be used directly in the preparation of a number of cytotoxic maytansinoid-cell binding agent conjugates.
  • maytansinoid derivative 6 is used in the production of novel maytansinoids having a disulfide moiety that bears a reactive group, using the novel methods set forth above in Schemes 2a and 3a.
  • Maytansinoid derivative 6 may be synthesized by disulfide exchange between DM 1 and 4-(2-pyridyldithio)-pentanoic acid (compound 5 ).
  • a solution of 4-(2-pyridyldithio)-pentanoic acid in methanol is treated with a solution of DM 1 in methanol.
  • Potassium phosphate buffer is added, and the reaction mixture is stirred under an argon atmosphere at room temperature.
  • the progress of the reaction may be monitored by HPLC.
  • the product 6 may be purified by HPLC.
  • the purified product may be re-analyzed by HPLC.
  • the identity of the product may be established by high resolution mass spectrometry of the sodium salt of 6.
  • Maytansinoid derivative 6 may be prepared by an alternative method wherein maytansinol is coupled with the mixed disulfide of N-methyl-N-(3-mercaptopropanoyl)-L-alanine and trimethylsilylethyl 4-mercaptopentanoate (compound 9 ) to yield the maytansinoid ester (compound 10 ), which is then deprotected to yield compound 6 .
  • Cell binding agents may be of any kind presently known, or that become known and include peptides and non-peptides. Generally, these can be antibodies (especially monoclonal antibodies), lymphokines, hormones, growth factors, vitamins, nutrient-transport molecules (such as transferrin), or any other cell binding molecule or substance.
  • cell binding agents that can be used include:
  • interferons e.g. alpha., beta., gamma.
  • lymphokines such as IL-2, IL-3, IL-4, IL-6;
  • hormones such as insulin, TRH (thyrotropin releasing hormone), MSH (melanocyte-stimulating hormone), steroid hormones, such as androgens and estrogens;
  • EGF EGF
  • TGF-alpha FGF
  • FGF FGF
  • VEGF vascular endothelial growth factor
  • G-CSF G-CSF
  • M-CSF M-CSF
  • GM-CSF GM-CSF
  • vitamins such as folate.
  • Monoclonal antibody techniques allow for the production of extremely specific cell binding agents in the form of specific monoclonal antibodies.
  • Particularly well known in the art are techniques for creating monoclonal antibodies produced by immunizing mice, rats, hamsters or any other mammal with the antigen of interest such as the intact target cell, antigens isolated from the target cell, whole virus, attenuated whole virus, and viral proteins such as viral coat proteins.
  • Sensitized human cells can also be used.
  • Another method of creating monoclonal antibodies is the use of phage libraries of scFv (single chain variable region), specifically human scFv (see e.g., Griffiths et al., U.S. Pat. Nos.
  • Selection of the appropriate cell binding agent is a matter of choice that depends upon the particular cell population that is to be targeted, but in general human monoclonal antibodies are preferred if an appropriate one is available.
  • the monoclonal antibody J5 is a murine IgG 2a antibody that is specific for the Common Acute Lymphoblastic Leukemia Antigen (CALLA) (Ritz et al. Nature 283:583-585 (1980)) and can be used if the target cells express CALLA such as in the disease of acute lymphoblastic leukemia.
  • the monoclonal antibody anti-B4 is a murine IgG 1 , that binds to the CD19 antigen on B cells (Nadler et al. J. Immunol. 131:244-250 (1983)) and can be used if the target cells are B cells or diseased cells that express this antigen such as in non-Hodgkin's lymphoma or chronic lymphoblastic leukemia.
  • GM-CSF which binds to myeloid cells can be used as a cell binding agent to diseased cells from acute myelogenous leukemia.
  • IL-2 which binds to activated T-cells can be used for prevention of transplant graft rejection, for therapy and prevention of graft-versus-host disease, and for treatment of acute T-cell leukemia.
  • MSH which binds to melanocytes can be used for the treatment of melanoma.
  • Cancers of the breast and testes can be successfully targeted with estrogen (or estrogen analogues) or androgen (or androgen analogues) respectively as cell binding agents.
  • huN 901 antibody 2.5 mg/mL
  • aqueous buffer 50 mM potassium phosphate, 50 mM sodium chloride, 2 mM ethylenediaminetetraacetic acid disodium salt
  • DMA dimethylacetamide
  • the reaction was allowed to proceed for 13 h at ambient temperature.
  • the reaction mixture was split into two portions. One portion was purified by passage over a Sephadex G 25 gel filtration column, and the second portion was purified over a Sephacryl S 300 gel filtration column. In each case the fractions containing monomeric conjugate were pooled.
  • huN 901 antibody 2.5 mg/mL
  • aqueous buffer 50 mM potassium phosphate, 50 mM sodium chloride, 2 mM ethylenediaminetetraacetic acid disodium salt
  • DMA dimethylacetamide
  • the reaction was allowed to proceed for 11 h at ambient temperature.
  • the reaction mixture was split into two portions. One portion was purified by passage over a Sephadex G 25 gel filtration column, and the second portion was purified over a Sephacryl S 300 gel filtration column. In each case the fractions containing monomeric conjugate were pooled.
  • the mixture was diluted with 700 mL of deionized water and extracted with a 1:1 solution of ethyl acetate:hexanes (2 ⁇ 1.4 L). The organic layers were combined and washed sequentially with 700 mL deionized water and 700 mL saturated aqueous sodium chloride. The solvent was evaporated under reduced pressure ( ⁇ 15 Torr). The residue was dissolved in 210 mL of reagent grade ethanol and transferred to a 1 L flask. Deionized water (210 mL) and thiourea (66.4 g, 0.87 mol) were then added to the flask. The flask was equipped with a reflux condenser and was heated in an oil bath with stirring to give a mild reflux.
  • N 2 ′-deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine (L-DM 1 -TPA, 6): A solution of 4-(2-pyridyldithio)-pentanoic acid (5, 24 mg, 0.10 mmol) and L-DM 1 (1, 30 mg, 0.041 mmol) in glass distilled methanol (5 mL) was vigorously stirred, and 3 mL of an aqueous buffer (200 mM KH 2 PO 4 , 2 mM EDTA, pH 7.6) was added dropwise.
  • an aqueous buffer 200 mM KH 2 PO 4 , 2 mM EDTA, pH 7.6
  • reaction was left overnight and product was purified by HPLC using a Vydac C-18, 10 ⁇ 250 mm column, 30° C., flow rate 4.75 mL/min with a linear gradient of acetonitrile (15% to 85% over 30 min) in 40 mM ammonium acetate buffer, pH 7.2.
  • L-DM 1 -TPA (6) eluted with a retention time of 12 min.
  • the product was collected as the ammonium salt and was taken up in 15 mL of ethyl acetate. The solution was washed successively with 4 mL of 1 M HCl followed by 3 mL of saturated sodium chloride.
  • N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine N-succinimidyl ester (L-DM 1 -TPA succinimidyl ester, 2): A solution of L-DM 1 -TPA (6) (10 mg, 0.011 mmol) in methylene chloride (1.5 mL) was treated with N-hydroxysuccinimide (10 mg, 0.086 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide.HCl (21 mg, 0.11 mmol) with vigorous stirring.
  • N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine N-succinimidyl ester (L-DM 1 -TPA succinimidyl ester, 2): A solution of N-succinimidyl ester of 4-(2-pyridyldithio)-pentanoic acid (SPP, 7 , 3 mg, 15 ⁇ mol) in methanol (15 ml) was reacted with DM 1 (1, 0.58 mg, 0.8 ⁇ mol) in dimethylacetamide (0.1 ml).
  • Potassium phosphate buffer (0.5 ml of a 0.2 M solution, pH 6, 2 mM EDTA) was added, and the reaction mixture was stirred under an argon atmosphere at room temperature. The progress of the reaction was monitored by silica gel TLC and the product was purified by preparatory silica gel TLC as described above.
  • N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine N-sulfosuccinimidyl ester (L-DM 1 -TPA sulfosuccinimidyl ester, 3 a ): L-DM 1 -TPA (6, 2 mg 0.002 mmol) was dissolved in dimethylacetamide (0.25 mL), to which N-hydroxysulfosuccinimide sodium salt (1.0 mg, 0.0046 mmol) and dicyclohexylcarbodiimide (1.0 mg, 0.0048 mmol) were added.
  • N 2′ -deacetyl-N 2′ -[3-(3-carboxy-1-methyl-propyldithio)-1-oxopropyl]-maytansine (L-DM 1 -TPA, 6) and 4-(2-pyridyldithio)-pentanoic acid (PPA, 5 ) were as set forth in Example 2a above.
  • Maytansinoid 3 a can also be prepared directly by reaction of DM 1 ( 1 ) with the sodium salt of sulfoSPP (N-sulfosuccinimidyl ester of 4-(2-pyridyldithio)-pentanoic acid).
  • the sodium salt of sulfoSPP ( 8 a ) can be prepared by coupling of PPA ( 5 ) with the sodium salt of N- hydroxysulfosuccinimde in the presence of EDC.HCl, by the method described for SPP ( 7 ) (see Example 2a above).
  • Maytansinoid 6 can also be directly prepared from maytansinol as outlined in FIG. 5 .
  • Compound 9 is prepared by disulfide exchange between the (2-trimethylsilyl)ethyl ester of PPA ( 5 ) and N-methyl-N-(3-mercapto-1-oxopropyl)-L-alanine.
  • the product can be purified by column chromatography on silica gel. Esterification of maytansinol with 6 equivalents of 9 in the presence of DCC (7.2 eq) and dimethylaminopyridine (DMAP) or zinc chloride (1 eq) in dichloromethane, as previously described (U.S. Pat. No.
  • maytansinoid 10 which can be purified by standard chemical means, such as silica gel chromatography or HPLC.
  • treatment of 10 with 5 equivalents of tetrabutylammonium fluoride in tetrahydrofuran for 30 min. at room temperature results in cleavage of the (trimethylsilyl)ethyl protecting group to yield 6, which can be purified by HPLC as described in Example 2a.
  • the huN 901 -DM 1 conjugates prepared by this new, one step method were evaluated for in vitro cytotoxicity towards antigen-expressing cells as follows.
  • a clone of A431 cells constitutively expressing the antigen for huN 901 (NCAM/CD56) were used in this assay.
  • Cells were plated into 6-well tissue-culture treated plates at a density of 2 ⁇ 10 3 cells/well in 2 ml of DMEM medium supplemented with 10% fetal calf serum and penicillin+streptomycin.
  • a huN 901 -DM 1 conjugate or the control huN 901 antibody was added to the wells at the time of plating, and the cultures were incubated in a tissue culture incubator at 37° C., 6% CO 2 , for 5 to 7 days to form colonies not smaller than 25 cells/colony.
  • the plates were then washed with PBS, and then fixed/stained for 30 min at room temperature with 10% formaldehyde/0.2% (w/v) Crystal Violet in PBS.
  • the wells were rinsed 3 times with water, dried by air, and the colonies were counted under a dissection low magnification microscope. The surviving fractions were calculated as the number of colonies in drug-treated well/number of colonies in non-treated well.
  • FIG. 1 The results indicate that huN 901 -DM 1 conjugates prepared by the one-step method using maytansinoid 2 , followed by purification either by Sephadex G 25 or Sephacryl S 300 chromatography were potent in killing antigen positive cells, with an IC 50 value of 1 ⁇ 10 ⁇ 10 M. In contrast, the unconjugated huN 901 antibody was non-toxic.

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Transplantation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
US09/867,598 2001-05-31 2001-05-31 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents Expired - Lifetime US6441163B1 (en)

Priority Applications (20)

Application Number Priority Date Filing Date Title
US09/867,598 US6441163B1 (en) 2001-05-31 2001-05-31 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
NZ523655A NZ523655A (en) 2001-05-31 2002-02-14 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
JP2003502004A JP5190170B2 (ja) 2001-05-31 2002-02-14 メイタンシノイドと細胞結合剤との細胞傷害性コンジュゲートを製造する方法
PT02720913T PT1390370E (pt) 2001-05-31 2002-02-14 Processos de preparação de conjugados citotóxicos à base de maitansinóides e de agentes de fixação das células
ES11003908.8T ES2551233T3 (es) 2001-05-31 2002-02-14 Métodos para la preparación de conjugados citotóxicos de maitansinoides y agentes que se fijan a las células
EP02720913.9A EP1390370B1 (fr) 2001-05-31 2002-02-14 Procedes de preparation de conjugues cytotoxiques a base de maytansinoides et d'agents de fixation des cellules
ES02720913.9T ES2574640T3 (es) 2001-05-31 2002-02-14 Métodos para la preparación de conjugados citotóxicos de maitansinoides y agentes que se fijan a las células
PCT/US2002/003378 WO2002098883A1 (fr) 2001-05-31 2002-02-14 Procedes de preparation de conjugues cytotoxiques a base de maytansinoides et d'agents de fixation des cellules
PT110039088T PT2348024E (pt) 2001-05-31 2002-02-14 Preparação de ácido biliar sintético
AU2002251880A AU2002251880B2 (en) 2001-05-31 2002-02-14 Method for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
EP11003908.8A EP2348024B1 (fr) 2001-05-31 2002-02-14 Procédé de préparation de conjugués cytotoxiques de maytansinoïdes et agents de liaison de cellules
DK02720913.9T DK1390370T3 (en) 2001-05-31 2002-02-14 PROCESSES FOR PREPARING cytotoxic conjugates of maytansinoids AND CELL BINDING AGENTS
CA2417858A CA2417858C (fr) 2001-05-31 2002-02-14 Procedes de preparation de conjugues cytotoxiques a base de maytansinoides et d'agents de fixation des cellules
DK11003908.8T DK2348024T3 (en) 2001-05-31 2002-02-14 PROCEDURES FOR PREPARING CYTOTOXIC CONJUGATES OF MAYTANSINOIDS AND CELL BINDING AGENTS
US10/161,651 US7368565B2 (en) 2001-05-31 2002-06-05 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
HK04103250.5A HK1060355A1 (zh) 2001-05-31 2004-05-10 美登素類和細胞結合劑的細胞毒性偶聯物的製備方法
HK11107839.7A HK1149765A1 (en) 2001-05-31 2004-05-10 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
JP2010085225A JP5271302B2 (ja) 2001-05-31 2010-04-01 メイタンシノイドと細胞結合剤との細胞傷害性コンジュゲート
CY20151100954T CY1116855T1 (el) 2001-05-31 2015-10-26 Μεθοδοι για την παρασκευη κυτταροτοξικων συζευγματων μεϋτανσινοειδων και παραγοντων δεσμευσης κυτταρων
CY20161100623T CY1117729T1 (el) 2001-05-31 2016-07-05 Μεθοδοι για την παρασκευη κυτταροτοξικων συζευγματων μεϋτανσινοειδων και παραγοντων δεσμευσης κυτταρου

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US09/867,598 US6441163B1 (en) 2001-05-31 2001-05-31 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/161,651 Division US7368565B2 (en) 2001-05-31 2002-06-05 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents

Publications (1)

Publication Number Publication Date
US6441163B1 true US6441163B1 (en) 2002-08-27

Family

ID=25350107

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/867,598 Expired - Lifetime US6441163B1 (en) 2001-05-31 2001-05-31 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US10/161,651 Expired - Fee Related US7368565B2 (en) 2001-05-31 2002-06-05 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents

Family Applications After (1)

Application Number Title Priority Date Filing Date
US10/161,651 Expired - Fee Related US7368565B2 (en) 2001-05-31 2002-06-05 Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents

Country Status (12)

Country Link
US (2) US6441163B1 (fr)
EP (2) EP2348024B1 (fr)
JP (2) JP5190170B2 (fr)
AU (1) AU2002251880B2 (fr)
CA (1) CA2417858C (fr)
CY (2) CY1116855T1 (fr)
DK (2) DK1390370T3 (fr)
ES (2) ES2551233T3 (fr)
HK (2) HK1060355A1 (fr)
NZ (1) NZ523655A (fr)
PT (2) PT2348024E (fr)
WO (1) WO2002098883A1 (fr)

Cited By (340)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030055226A1 (en) * 2001-05-31 2003-03-20 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US20030108966A1 (en) * 2001-10-16 2003-06-12 Mather Jennie P. Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
US20030138425A1 (en) * 2001-09-21 2003-07-24 Mather Jennie Powell Antibodies that bind to cancer-associated antigen cytokeratin 8 and methods of use thereof
US20040014980A1 (en) * 2000-09-12 2004-01-22 Smithkline Beecham Plc Process and intermediates
US20040037833A1 (en) * 2002-06-19 2004-02-26 Mather Jennie P. Novel RAAG10 cell surface target and a family of antibodies recognizing that target
WO2004016801A2 (fr) * 2002-08-16 2004-02-26 Immunogen, Inc. Agents de reticulation a reactivite et solubilite elevees et utilisation de ceux-ci dans la preparation de conjugues pour l'administration ciblee de medicaments a petites molecules
US20040048312A1 (en) * 2002-04-12 2004-03-11 Ronghao Li Antibodies that bind to integrin alpha-v-beta-6 and methods of use thereof
US20040048319A1 (en) * 2002-05-03 2004-03-11 Mather Jennie P. ALCAM and ALCAM modulators
US20040072997A1 (en) * 2000-12-20 2004-04-15 Alsobrook John P. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20040171814A1 (en) * 2002-11-13 2004-09-02 Mather Jennie P. Antigen PIPA and antibodies that bind thereto
WO2004084823A2 (fr) 2003-03-19 2004-10-07 Abgenix, Inc. Anticorps contre l'antigene de lymphocytes t, du domaine d'immunoglobuline et du domaine 1 de mucine (tim-1) et leurs utilisations
US20040241174A1 (en) * 2003-05-14 2004-12-02 Immunogen, Inc. Drug conjugate composition
US20050031617A1 (en) * 2003-06-06 2005-02-10 Jing Ma Antibodies specific for cancer associated antigen SM5-1 and uses thereof
US20050053608A1 (en) * 2003-06-27 2005-03-10 Richard Weber Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
WO2005028498A2 (fr) 2003-09-18 2005-03-31 Raven Biotechnologies, Inc. Kid3 et anticorps de liaison a kid3
WO2005037992A2 (fr) 2003-10-10 2005-04-28 Immunogen, Inc. Procede de ciblage de populations cellulaires specifiques a l'aide de conjugues formes d'un agent de liaison cellulaire et de maytansinoides, lies par l'intermediaire d'un lieur non clivable, lesdits conjugues et leurs procedes de preparation
WO2005044998A2 (fr) 2003-11-05 2005-05-19 Palingen, Inc. Cytotoxicite augmentee de l'anticorps de liaison cdim contre les lymphocytes b
US20050113571A1 (en) * 2001-03-16 2005-05-26 Smithkline Beecham Corporation Process for preparing maytansinol
US20050170475A1 (en) * 2003-05-08 2005-08-04 Immunogen Methods for the production of ansamitocins
US20050232926A1 (en) * 2003-06-06 2005-10-20 Oncomax Acquisition Corp. Antibodies specific for cancer associated antigen SM5-1 and uses thereof
US20050276812A1 (en) * 2004-06-01 2005-12-15 Genentech, Inc. Antibody-drug conjugates and methods
US20050287155A1 (en) * 2004-06-15 2005-12-29 Santi Daniel V Conjugates with reduced adverse systemic effects
US20060039908A1 (en) * 2004-06-07 2006-02-23 Mather Jennie P Transferrin receptor antibodies
USRE39151E1 (en) 2000-08-18 2006-06-27 Immunogen, Inc. Process for the preparation and purification of thiol-containing maytansinoids
US20060166291A1 (en) * 2005-01-12 2006-07-27 Mather Jennie P KID31 and antibodies that bind thereto
US20060171952A1 (en) * 2005-02-02 2006-08-03 Mather Jennie P JAM-3 and antibodies that bind thereto
US20060172350A1 (en) * 2005-02-02 2006-08-03 Mather Jennie P ADAM-9 modulators
US20060172349A1 (en) * 2005-01-31 2006-08-03 Mather Jennie P LUCA2 and antibodies that bind thereto
WO2006084226A2 (fr) 2005-02-04 2006-08-10 Raven Biotechnologies, Inc. Anticorps se liant a epha2 et procedes d'utilisation de ceux-ci
WO2006086733A2 (fr) 2005-02-11 2006-08-17 Immunogen, Inc. Procede pour preparer des conjugues medicamenteux stables
US20060233814A1 (en) * 2005-04-15 2006-10-19 Immunogen Inc. Elimination of heterogeneous or mixed cell population in tumors
WO2004103272A3 (fr) * 2003-05-20 2006-11-23 Immunogen Inc Agents cytotoxiques ameliores contenant de nouveaux maytansinoides
US20070031402A1 (en) * 2005-08-03 2007-02-08 Immunogen Inc. Immunoconjugate formulations
US20070048314A1 (en) * 2005-08-24 2007-03-01 Immunogen, Inc. Process for preparing purified drug conjugates
EP1806365A1 (fr) 2006-01-05 2007-07-11 Boehringer Ingelheim International GmbH Anticorps spécifiques pour la protéine alpha d'activation de fibroblastes et leurs immunoconjugués
US20070270585A1 (en) * 2003-05-20 2007-11-22 Immunogen, Inc. Cytotoxic agents comprising new maytansinoids
US20080050310A1 (en) * 2006-05-30 2008-02-28 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
WO2008066691A2 (fr) 2006-11-08 2008-06-05 Macrogenics West, Inc. Tes7, et anticorps se liant à celui-ci
US20090011060A1 (en) * 2007-07-06 2009-01-08 Peter Koepke Campsiandra angustifolia extract and methods of extracting and using such extract
US20090017140A1 (en) * 2007-07-09 2009-01-15 Peter Koepke Maytenus abenfolia extract and methods of extracting and using such extract
US20090035395A1 (en) * 2007-08-01 2009-02-05 Peter Koepke Spondias mombin l. extract and methods of extracting and using such extract
US20090074891A1 (en) * 2007-09-18 2009-03-19 Peter Koepke Combretum laurifolium mart. extract and methods of extracting and using such extract
US20090099336A1 (en) * 2003-07-21 2009-04-16 Immunogen Inc. CA6 Antigen-Specific Cytotoxic Conjugate and Methods of Using the Same
US7572896B2 (en) 2005-02-03 2009-08-11 Raven Biotechnologies, Inc. Antibodies to oncostatin M receptor
US20100047257A1 (en) * 2006-07-18 2010-02-25 Sanofi-Aventis Antagonist antibody for the treatment of cancer
US20100129314A1 (en) * 2008-04-30 2010-05-27 Immunogen Inc. Potent conjugates and hydrophilic linkers
US20100136033A1 (en) * 2000-03-16 2010-06-03 Immunogen, Inc. METHODS OF TREATMENT USING ANTI-ErbB ANTIBODY-MAYTANSINOID CONJUGATES
WO2010091150A1 (fr) 2009-02-05 2010-08-12 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
EP2241577A1 (fr) 2007-08-09 2010-10-20 Boehringer Ingelheim International GmbH Anticorps anti-CD37
WO2010126551A1 (fr) 2009-04-30 2010-11-04 Immunogen, Inc. Conjugués puissants et séquences de liaison hydrophiles
WO2010141566A1 (fr) 2009-06-03 2010-12-09 Immunogen, Inc. Procédés de conjugaison
WO2010141902A2 (fr) 2009-06-04 2010-12-09 Novartis Ag Procédés d'identification de sites pour la conjugaison d'igg
US20110045005A1 (en) * 2001-10-19 2011-02-24 Craig Crowley Compositions and methods for the treatment of tumor of hematopoietic origin
EP2298806A1 (fr) 2002-10-16 2011-03-23 Purdue Pharma L.P. Anticorps se fixant sur des polypeptides CA 125/0722P associés à des cellules et leurs procédés d'utilisation
EP2305716A2 (fr) 2004-11-30 2011-04-06 Curagen Corporation Anticorps diriges contre la gpnmb et leurs utilisations
WO2011039724A1 (fr) 2009-10-02 2011-04-07 Sanofi-Aventis Anticorps qui se lient spécifiquement au récepteur epha2
EP2311880A2 (fr) 2005-01-05 2011-04-20 Biogen Idec MA Inc. Molécules à crypto-liaison
WO2011069074A2 (fr) 2009-12-04 2011-06-09 Genentech, Inc. Procédés de traitement de cancer du sein métastasique avec trastuzumab-mcc-dm1
EP2332992A1 (fr) 2004-03-23 2011-06-15 Biogen Idec MA Inc. Agents de couplage de récepteur et leurs utilisations thérapeutiques
US20110166319A1 (en) * 2005-02-11 2011-07-07 Immunogen, Inc. Process for preparing purified drug conjugates
WO2011100403A1 (fr) 2010-02-10 2011-08-18 Immunogen, Inc Anticorps anti-cd20 et utilisations de ceux-ci
WO2011109400A2 (fr) 2010-03-04 2011-09-09 Macrogenics,Inc. Anticorps réagissant avec b7-h3, fragments immunologiquement actifs associés et utilisations associées
EP2384767A1 (fr) 2005-03-24 2011-11-09 Millennium Pharmaceuticals, Inc. Anticorps se liant à l'OV064 et leurs procédés d'utilisation
WO2011153346A1 (fr) 2010-06-03 2011-12-08 Genentech, Inc. Imagerie par immuno-tep d'anticorps et d'immunoconjugués et utilisations correspondantes
WO2011156328A1 (fr) 2010-06-08 2011-12-15 Genentech, Inc. Anticorps et conjugués modifiés par la cystéine
WO2012016227A2 (fr) 2010-07-29 2012-02-02 Xencor, Inc. Anticorps dont les points isoélectriques sont modifiés
WO2012019024A2 (fr) 2010-08-04 2012-02-09 Immunogen, Inc. Molécules se liant à her3 et leurs immunoconjugués
CN101374545B (zh) * 2005-04-15 2012-03-28 免疫基因公司 消除肿瘤中的异质或混合细胞群体
WO2012045085A1 (fr) 2010-10-01 2012-04-05 Oxford Biotherapeutics Ltd. Anticorps anti-ror1
WO2012047724A1 (fr) 2010-09-29 2012-04-12 Agensys, Inc. Conjugués anticorps-médicaments (adc) se liant aux protéines 191p4d12
WO2012065161A2 (fr) 2010-11-12 2012-05-18 Scott & White Healthcare Anticorps contre le marqueur 8 endothélial tumoral
WO2012074757A1 (fr) 2010-11-17 2012-06-07 Genentech, Inc. Conjugués d'anticorps alaninyl-maytansinol
WO2012078771A1 (fr) 2010-12-09 2012-06-14 Genentech, Inc. Traitement de cancer her2-positif avec du paclitaxel et du trastuzumab-mcc-dm1
WO2012092539A2 (fr) 2010-12-31 2012-07-05 Takeda Pharmaceutical Company Limited Anticorps contre dll4 et leurs utilisations
WO2012092616A1 (fr) 2010-12-30 2012-07-05 Takeda Pharmaceutical Company Limited Anticorps anti-cd38 conjugués
WO2012109624A2 (fr) 2011-02-11 2012-08-16 Zyngenia, Inc. Complexes plurispécifiques monovalents et multivalents et leurs utilisations
WO2012112708A1 (fr) 2011-02-15 2012-08-23 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et procédés de préparation
US20120253021A1 (en) * 2011-03-29 2012-10-04 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
WO2012162561A2 (fr) 2011-05-24 2012-11-29 Zyngenia, Inc. Complexes plurispécifiques multivalents et monovalents, et leurs utilisations
WO2012162067A2 (fr) 2011-05-21 2012-11-29 Macrogenics, Inc. Molécules de liaison des cd3 capables de se lier aux cd3 humaines et non humaines
WO2012171020A1 (fr) 2011-06-10 2012-12-13 Mersana Therapeutics, Inc. Conjugués de médicament-protéine-polymère
WO2012177837A2 (fr) 2011-06-21 2012-12-27 Immunogen, Inc. Nouveaux dérivés de maytansinoïde comprenant un lieur peptidique et conjugués correspondants
USRE43899E1 (en) 1999-10-01 2013-01-01 Immunogen Inc. Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
EP2548583A2 (fr) 2005-11-10 2013-01-23 Curagen Corporation Methode de traitement du cancer de l'ovaire et du rein utilisant des anticorps diriges contre l'antigene a domaine 1 de mucine et a domaine immunoglobuline des lymphocytes t (tim-1)
WO2013012733A1 (fr) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Régions fc hétérodimères, molécules de liaison les comprenant, et méthodes associées
WO2013022855A1 (fr) 2011-08-05 2013-02-14 Xencor, Inc. Anticorps avec points isoélectriques modifiés et immunofiltration
WO2013033380A1 (fr) 2011-08-31 2013-03-07 Genentech, Inc. Marqueurs de diagnostic
WO2013055809A1 (fr) 2011-10-10 2013-04-18 Xencor, Inc. Procédé de purification d'anticorps
WO2013063001A1 (fr) 2011-10-28 2013-05-02 Genentech, Inc. Associations thérapeutiques et méthodes de traitement du mélanome
WO2013075048A1 (fr) 2011-11-16 2013-05-23 Amgen Inc. Procédé de traitement de troubles associés au mutant de délétion viii du récepteur du facteur de croissance épidermique
WO2013083817A1 (fr) 2011-12-08 2013-06-13 Biotest Ag Utilisations d'immunoconjugués ciblant cd138
WO2013106485A2 (fr) 2012-01-09 2013-07-18 The Scripps Research Institute Régions déterminant la complémentarité ultralongues et utilisations associées
WO2013106489A1 (fr) 2012-01-09 2013-07-18 The Scripps Research Institute Anticorps humanisés à cdr3 ultralongues
WO2013109994A1 (fr) 2012-01-20 2013-07-25 Sea Lane Biotechnologies, Llc Conjugués surrobody
WO2013130093A1 (fr) 2012-03-02 2013-09-06 Genentech, Inc. Biomarqueurs pour un traitement à base de composés chimiothérapeutiques anti-tubuline
EP2638907A2 (fr) 2008-03-18 2013-09-18 Genentech, Inc. Combinaisons de conjugué de médicament-anticorps anti-HER2 et du lapatinib
WO2013149159A1 (fr) 2012-03-30 2013-10-03 Genentech, Inc. Anticorps et immunoconjugués anti-lgr5
WO2013160396A1 (fr) 2012-04-26 2013-10-31 Boehringer Ingelheim International Gmbh Combinaison d'anticorps cd37 avec la bendamustine
WO2013165940A1 (fr) 2012-05-01 2013-11-07 Genentech, Inc. Anticorps anti-pmel17 et immunoconjugués
WO2013171287A1 (fr) 2012-05-16 2013-11-21 Boehringer Ingelheim International Gmbh Combinaison d'anticorps anti-cd37 avec ice (ifosmamide, carboplatine, etoposide)
WO2013171289A1 (fr) 2012-05-16 2013-11-21 Boehringer Ingelheim International Gmbh Combinaison d'anticorps anti-cd37 avec d'autres agents
WO2013182668A1 (fr) 2012-06-08 2013-12-12 F. Hoffmann-La Roche Ag Sélectivité mutante et associations d'un inhibiteur de phospho‑inositide 3 kinase et agents chimiothérapeutiques pour le traitement du cancer
WO2014055877A1 (fr) 2012-10-04 2014-04-10 Immunogen, Inc. Utilisation d'une membrane de pvdf pour purifier des conjugués d'agent de liaison cellulaire-agent cytotoxique
WO2014089335A2 (fr) 2012-12-07 2014-06-12 Amgen Inc. Protéines de liaison à l'antigène bcma
WO2014093379A1 (fr) 2012-12-10 2014-06-19 Mersana Therapeutics, Inc. Composés auristatine et leurs conjugués
WO2014093394A1 (fr) 2012-12-10 2014-06-19 Mersana Therapeutics, Inc. Conjugués protéine-polymère-médicament
WO2014093640A1 (fr) 2012-12-12 2014-06-19 Mersana Therapeutics,Inc. Conjugués hydroxy-polymère-médicament-protéine
WO2014113510A1 (fr) 2013-01-15 2014-07-24 Xencor, Inc. Elimination rapide de complexes antigéniques à l'aide de nouveaux anticorps
US8790649B2 (en) 2010-10-29 2014-07-29 Immunogen, Inc. EGFR-binding molecules and immunoconjugates thereof
WO2014134486A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014134483A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014145806A2 (fr) 2013-03-15 2014-09-18 Xencor, Inc. Protéines hétérodimériques
WO2014145090A1 (fr) 2013-03-15 2014-09-18 Regeneron Pharmaceuticals, Inc. Molécules biologiquement actives, leurs conjugués, et utilisations thérapeutiques
WO2014144466A1 (fr) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anticorps anti-alpha ν bêta 6 et leurs utilisations
WO2014143739A2 (fr) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anticorps anti-alpha ν bêta 6 et leurs utilisations
US8840889B2 (en) 2009-08-13 2014-09-23 The Johns Hopkins University Methods of modulating immune function
WO2014159835A1 (fr) 2013-03-14 2014-10-02 Genentech, Inc. Anticorps et immunoconjugués anti-b7-h4
WO2014160160A2 (fr) 2013-03-13 2014-10-02 Novartis Ag Conjugués anticorps-médicaments
WO2014182970A1 (fr) 2013-05-08 2014-11-13 Zymeworks Inc. Constructions de liaison aux antigènes her2 et her3 bispécifiques
WO2014194030A2 (fr) 2013-05-31 2014-12-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
WO2014210267A1 (fr) * 2013-06-28 2014-12-31 Immunogen, Inc. Purification d'intermédiaires utilisés pour préparer des lieurs hétérobifonctionnels
WO2015000062A1 (fr) 2013-07-05 2015-01-08 Avidbiologics Inc. Conjugués d'anticorps anti-egfr
WO2015010100A2 (fr) 2013-07-18 2015-01-22 Fabrus, Inc. Anticorps humanisés comprenant des régions déterminant la complémentarité ultralongues
WO2015017552A1 (fr) 2013-08-01 2015-02-05 Agensys, Inc. Conjugués anticorps-médicament (adc) se liant à la protéine cd37
WO2015017146A2 (fr) 2013-07-18 2015-02-05 Fabrus, Inc. Anticorps à régions de détermination de complémentarité ultralongues
EP2845866A1 (fr) 2006-10-27 2015-03-11 Genentech, Inc. Anticorps et immuno-conjugués et utilisations associées
WO2015042108A1 (fr) 2013-09-17 2015-03-26 Genentech, Inc. Procédés d'utilisation d'anticorps anti-lgr5
WO2015054669A1 (fr) 2013-10-11 2015-04-16 Asana Biosciences, Llc Conjugués médicament-polymère-protéine
WO2015052537A1 (fr) 2013-10-11 2015-04-16 Oxford Biotherapeutics Ltd Anticorps conjugué contre ly75 pour le traitement du cancer
WO2015054400A2 (fr) 2013-10-08 2015-04-16 Immunogen, Inc. Schémas posologiques d'immunoconjugués anti-folr1
WO2015054659A1 (fr) 2013-10-11 2015-04-16 Mersana Therapeutics, Inc. Conjugués de médicament-protéine-polymère
US9023356B2 (en) 2007-03-15 2015-05-05 Ludwig Institute For Cancer Research Ltd Treatment method using EGFR antibodies and SRC inhibitors and related formulations
WO2015069922A2 (fr) 2013-11-06 2015-05-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps anti-alk, conjugues, et recepteurs antigeniques chimeriques, et leur utilisation
WO2015073721A1 (fr) 2013-11-13 2015-05-21 Zymeworks Inc. Produits de recombinaison liant un antigène monovalent et ciblant l'egfr et/ou l'her2 et leurs utilisations
WO2015089344A1 (fr) 2013-12-13 2015-06-18 Genentech, Inc. Anticorps et immunoconjugués anti-cd33
WO2015095227A2 (fr) 2013-12-16 2015-06-25 Genentech, Inc. Composés peptidomimétiques et conjugués anticorps-médicament de ceux-ci
WO2015094900A1 (fr) 2013-12-18 2015-06-25 Imclone Llc Composés contre le récepteur 3 du facteur de croissance des fibroblastes (fgfr3) et utilisations thérapeutiques
US9072798B2 (en) 2009-02-18 2015-07-07 Ludwig Institute For Cancer Research Ltd. Specific binding proteins and uses thereof
US9090693B2 (en) 2007-01-25 2015-07-28 Dana-Farber Cancer Institute Use of anti-EGFR antibodies in treatment of EGFR mutant mediated disease
WO2015112909A1 (fr) 2014-01-24 2015-07-30 Genentech, Inc. Procédés d'utilisation d'anticorps anti-steap1 et immunoconjugués
WO2015127685A1 (fr) 2014-02-28 2015-09-03 Hangzhou Dac Biotech Co., Ltd Lieurs chargés et leurs utilisations pour la conjugaison
WO2015149077A1 (fr) 2014-03-28 2015-10-01 Xencor, Inc. Anticorps bispécifiques se liant à cd38 et cd3
WO2015151081A2 (fr) 2015-07-12 2015-10-08 Suzhou M-Conj Biotech Co., Ltd Lieurs de pontage pour la conjugaison d'une molécule de liaison cellulaire
WO2015164665A1 (fr) 2014-04-25 2015-10-29 Genentech, Inc. Méthodes de traitement du cancer du sein précoce avec du trastuzumab-mcc-dm1 et du pertuzumab
WO2015179658A2 (fr) 2014-05-22 2015-11-26 Genentech, Inc. Immunoconjugués et anticorps anti-gpc3
WO2016001485A1 (fr) 2014-06-30 2016-01-07 Glykos Finland Oy Dérivé de saccharide d'une charge utile toxique et conjugués d'anticorps de celui-ci
US9233171B2 (en) 2011-11-21 2016-01-12 Immunogen, Inc. Method of treatment of tumors that are resistant to EGFR antibody therapies by EGFR antibody cytotoxic agent conjugate
US9238690B2 (en) 2010-10-29 2016-01-19 Immunogen, Inc. Non-antagonistic EGFR-binding molecules and immunoconjugates thereof
US9238878B2 (en) 2009-02-17 2016-01-19 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
WO2016014984A1 (fr) 2014-07-24 2016-01-28 Xencor, Inc. Élimination rapide de complexes antigéniques à l'aide de nouveaux anticorps
WO2016024195A1 (fr) 2014-08-12 2016-02-18 Novartis Ag Conjugués médicament-anticorps anti-cdh6
WO2016036804A1 (fr) 2014-09-03 2016-03-10 Immunogen, Inc. Dérivés de benzodiazépine cytotoxique
US9283276B2 (en) 2007-08-14 2016-03-15 Ludwig Institute For Cancer Research Ltd. Monoclonal antibody 175 targeting the EGF receptor and derivatives and uses thereof
WO2016040856A2 (fr) 2014-09-12 2016-03-17 Genentech, Inc. Anticorps et conjugués modifiés génétiquement avec de la cystéine
WO2016040868A1 (fr) 2014-09-12 2016-03-17 Genentech, Inc. Anticorps anti-cll-1 et immunoconjugués
WO2016044396A1 (fr) 2014-09-17 2016-03-24 Genentech, Inc. Immunoconjugués comprenant des anticorps anti-her2 et des pyrrolobenzodiazépines
US9302015B2 (en) 2013-08-21 2016-04-05 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
WO2016075670A1 (fr) 2014-11-14 2016-05-19 Novartis Ag Conjugués anticorps-médicament
WO2016090157A1 (fr) 2014-12-04 2016-06-09 Celgene Corporation Conjugués de biomolécule
US9409976B2 (en) 2012-02-08 2016-08-09 Igm Biosciences, Inc. CDIM binding proteins and uses thereof
WO2016141387A1 (fr) 2015-03-05 2016-09-09 Xencor, Inc. Modulation de lymphocytes t avec des anticorps bispécifiques et des hybrides fc
WO2016145099A1 (fr) 2015-03-09 2016-09-15 Agensys, Inc. Conjugués anticorps-médicament (cam) se liant aux protéines flt3
US9458241B2 (en) 2004-11-05 2016-10-04 Igm Biosciences, Inc. Antibody induced cell membrane wounding
EP3088004A1 (fr) 2004-09-23 2016-11-02 Genentech, Inc. Anticorps et conjugués modifiés au niveau des cystéines
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
US9498543B2 (en) 2013-03-15 2016-11-22 Novartis Ag Antibody drug conjugates
AU2015201534B2 (en) * 2009-06-03 2016-11-24 Immunogen, Inc. Conjugation methods
WO2016196285A1 (fr) 2015-06-04 2016-12-08 Imclone Llc Thérapies utilisant des composés qui ciblent le récepteur 3 du facteur de croissance des fibroblastes (fgfr3)
WO2016196373A2 (fr) 2015-05-30 2016-12-08 Genentech, Inc. Procédés de traitement de cancer du sein métastatique her2 positif
WO2016201394A1 (fr) 2015-06-12 2016-12-15 Miltenyi Biotec Technology, Inc. Procédé de traitement de cancer à l'aide de lymphocytes t génétiquement modifiés
WO2016200676A1 (fr) 2015-06-08 2016-12-15 Immunogen, Inc. Combinaisons d'immunoconjugués anti-cd37 et d'anticorps anti-cd20
US9540438B2 (en) 2011-01-14 2017-01-10 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US9545451B2 (en) 2013-08-21 2017-01-17 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
US9562102B2 (en) 2001-05-11 2017-02-07 Ludwig Institute For Cancer Research Specific binding proteins and uses thereof
WO2017049149A1 (fr) 2015-09-17 2017-03-23 Immunogen, Inc. Combinaisons thérapeutiques comprenant des immunoconjugués anti-folr1
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
WO2017062952A1 (fr) 2015-10-09 2017-04-13 Miltenyi Biotec Technology, Inc. Récepteurs antigéniques chimériques et leurs procédés d'utilisation
WO2017064675A1 (fr) 2015-10-16 2017-04-20 Genentech, Inc. Conjugués médicamenteux à pont disulfure encombré
US9650446B2 (en) 2013-01-14 2017-05-16 Xencor, Inc. Heterodimeric proteins
WO2017087280A1 (fr) 2015-11-16 2017-05-26 Genentech, Inc. Procédés de traitement d'un cancer positif her2
WO2017091745A1 (fr) 2015-11-25 2017-06-01 Immunogen, Inc. Formulations pharmaceutiques et leurs procédés d'utilisation
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
EP3196212A1 (fr) 2010-02-24 2017-07-26 Immunogen, Inc. Anticorps de récepteur 1 de folate et immunoconjugués et leurs utilisations
WO2017197234A1 (fr) 2016-05-13 2017-11-16 Bioatla, Llc Anticorps anti-ror2, fragments d'anticorps, leurs immunoconjugués et utilisations correspondantes
WO2017194568A1 (fr) 2016-05-11 2017-11-16 Sanofi Schéma de traitement utilisant un anticorps immunoconjugué anti-muc1 à base de maytansinoïde pour le traitement des tumeurs
WO2017205741A1 (fr) 2016-05-27 2017-11-30 Genentech, Inc. Procédé bioanalytique pour la caractérisation de conjugués anticorps-médicament spécifiques d'un site
WO2017214456A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
WO2017214339A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
WO2017214458A2 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
WO2017214322A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
US9850320B2 (en) 2014-11-26 2017-12-26 Xencor, Inc. Heterodimeric antibodies to CD3 X CD20
US9856327B2 (en) 2014-11-26 2018-01-02 Xencor, Inc. Heterodimeric antibodies to CD3 X CD123
WO2018004338A1 (fr) 2016-06-27 2018-01-04 Tagworks Pharmaceuticals B.V. Tétrazine clivable utilisée dans l'activation de médicaments bio-orthogonaux
EP3266469A2 (fr) 2008-04-30 2018-01-10 ImmunoGen, Inc. Agents de réticulation et leurs utilisations
RU2644280C1 (ru) * 2016-12-12 2018-02-08 Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) Способ получения противоопухолевого коньюгата на основе человеческого сывороточного альбумина, содержащего терапевтические и контрастирующий агенты
WO2018045325A1 (fr) 2016-09-02 2018-03-08 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec des duocars
US9943606B2 (en) 2014-01-15 2018-04-17 Rutgers, The State University Of New Jersey Dendritic polypeptide-based nanocarriers for the delivery of therapeutic agents
EP3311846A1 (fr) 2014-09-02 2018-04-25 ImmunoGen, Inc. Procédés de formulation de compositions de conjugués anticorps-médicament
US9975956B2 (en) 2011-12-22 2018-05-22 I2 Pharmaceuticals, Inc. Surrogate binding proteins which bind DR4 and/or DR5
WO2018091724A1 (fr) 2016-11-21 2018-05-24 Cureab Gmbh Anticorps anti-gp73 et immunoconjugués
WO2018098258A2 (fr) 2016-11-23 2018-05-31 Immunogen, Inc. Sulfonation sélective de dérivés de benzodiazépine
WO2018098269A2 (fr) 2016-11-23 2018-05-31 Mersana Therapeutics, Inc. Lieurs contenant des peptides pour des conjugués anticorps-médicament
US10017561B2 (en) 2009-05-13 2018-07-10 I2 Pharmaceuticals, Inc. Neutralizing molecules to influenza viruses
WO2018129524A1 (fr) 2017-01-09 2018-07-12 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-mésothéline
WO2018142322A1 (fr) 2017-02-03 2018-08-09 Novartis Ag Conjugués anticorps-médicament anti-ccr7
US10059768B2 (en) 2014-09-12 2018-08-28 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
WO2018160539A1 (fr) 2017-02-28 2018-09-07 Immunogen, Inc. Dérivés de maytansinoïdes comprenant des lieurs peptidiques auto-immolables et conjugués correspondants
WO2018175988A1 (fr) 2017-03-24 2018-09-27 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-cd33
WO2018185618A1 (fr) 2017-04-03 2018-10-11 Novartis Ag Conjugués de médicament-anticorps anti-cdh6 et combinaisons d'anticorps anti-gitr et méthodes de traitement
US10100115B2 (en) 2014-02-14 2018-10-16 Macrogenics, Inc. Methods for the treatment of vascularizing cancers
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
WO2018195302A1 (fr) 2017-04-19 2018-10-25 Bluefin Biomedicine, Inc. Anticorps anti-vtcn1 et conjugués anticorps-médicament
WO2018195243A1 (fr) 2017-04-20 2018-10-25 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et leurs conjugués
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
WO2018237262A1 (fr) 2017-06-22 2018-12-27 Mersana Therapeutics, Inc. Procédés de production de matrices polymères transportant des médicaments, et conjugués protéine-polymère-médicament
EP3421495A2 (fr) 2013-03-15 2019-01-02 Xencor, Inc. Modulation de cellules t avec des anticorps bispécifiques et des fusions fc
USRE47194E1 (en) 2007-05-08 2019-01-08 Genentech, Inc. Cysteine engineered anti-MUC16 antibodies and antibody drug conjugates
EP3424530A1 (fr) 2013-03-15 2019-01-09 Zyngenia, Inc. Complexes multispécifiques monovalents et multivalents et leurs utilisations
USRE47223E1 (en) 2005-06-20 2019-02-05 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2019025983A1 (fr) 2017-08-01 2019-02-07 Medimmune, Llc Conjugué anticorps monoclonal-médicament dirigé contre bcma
WO2019028051A1 (fr) 2017-07-31 2019-02-07 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd19/cd20
US10214580B2 (en) 2007-03-27 2019-02-26 I2 Pharmaceuticals, Inc. Constructs and libraries comprising antibody surrogate light chain sequences
US10227410B2 (en) 2015-12-07 2019-03-12 Xencor, Inc. Heterodimeric antibodies that bind CD3 and PSMA
US10232051B2 (en) 2015-07-15 2019-03-19 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
WO2019055842A1 (fr) 2017-09-15 2019-03-21 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd19
WO2019079249A1 (fr) 2017-10-16 2019-04-25 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd22
EP3486248A1 (fr) 2012-09-26 2019-05-22 ImmunoGen, Inc. Procédés améliorés d'acylation de maytansinol
US10300140B2 (en) 2011-07-28 2019-05-28 I2 Pharmaceuticals, Inc. Sur-binding proteins against ERBB3
US10316088B2 (en) 2016-06-28 2019-06-11 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
EP3494996A1 (fr) 2012-08-23 2019-06-12 Agensys, Inc. Conjugués anticorps-médicament (adc) qui se lient aux protéines 158p1d7
EP3498735A1 (fr) 2006-10-19 2019-06-19 Sanofi Anticorps anti-cd38 pour le traitement de la leucemie
WO2019126464A2 (fr) 2017-12-20 2019-06-27 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du vih/sida par immunothérapie
WO2019133652A1 (fr) 2017-12-28 2019-07-04 Immunogen, Inc. Dérivés de benzodiazépine
EP3520816A2 (fr) 2009-10-23 2019-08-07 Millennium Pharmaceuticals, Inc. Molécules d'anticorps anti-gcc et compositions et procédés associés
WO2019175125A1 (fr) 2018-03-13 2019-09-19 F. Hoffmann-La Roche Ag Polythérapie avec des agonistes de 4-1 bb (cd137) ciblés
US10428155B2 (en) 2014-12-22 2019-10-01 Xencor, Inc. Trispecific antibodies
WO2019212356A1 (fr) 2018-05-04 2019-11-07 Tagworks Pharmaceuticals B .V. Tétrazines pour un rendement élevé de conjugaison de chimie click in vivo et un rendement élevé de libération de chimie click
WO2019212357A1 (fr) 2018-05-04 2019-11-07 Tagworks Pharmaceuticals B.V. Composés comprenant un lieur pour augmenter la stabilité de transcyclooctène
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
US10501543B2 (en) 2016-10-14 2019-12-10 Xencor, Inc. IL15/IL15Rα heterodimeric Fc-fusion proteins
US10509035B2 (en) 2015-08-07 2019-12-17 Gamamabs Pharma Sa Antibodies, antibody drug conjugates and methods of use
WO2019238843A1 (fr) 2018-06-14 2019-12-19 Berlin-Chemie Ag Associations pharmaceutiques
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
US10526417B2 (en) 2014-11-26 2020-01-07 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38
WO2020010079A2 (fr) 2018-07-02 2020-01-09 Amgen Inc. Protéine de liaison à l'antigène anti-steap1
US10570211B2 (en) 2011-01-24 2020-02-25 Gilead Sciences, Inc. Antibodies selective for cells presenting EGFR at high density
US10584181B2 (en) 2009-12-04 2020-03-10 Genentech, Inc. Methods of making and using multispecific antibody panels and antibody analog panels
EP3620470A1 (fr) 2013-10-11 2020-03-11 The United States of America, as represented by The Secretary, Department of Health and Human Services Anticorps tem8 et leur utilisation
EP3620467A1 (fr) 2010-03-12 2020-03-11 Debiopharm International SA Molécules de liaison cd37 et immunoconjugués correspondants
WO2020061498A1 (fr) 2018-09-20 2020-03-26 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer au moyen d'une immunothérapie anti-cd123
WO2020069184A2 (fr) 2018-09-26 2020-04-02 Lentigen Technology, Inc. Compositions et procédés de traitement du cancer par immunothérapie anti-cd19/cd22
WO2020081119A1 (fr) 2018-10-15 2020-04-23 Genentech, Inc. Méthodes de traitement de cancer du sein résiduel à l'aide de trastuzumab emtansine
US10640563B2 (en) 2016-06-08 2020-05-05 Abbvie Inc. Anti-B7-H3 antibodies and antibody drug conjugates
WO2020092385A1 (fr) 2018-10-29 2020-05-07 Mersana Therapeutics, Inc. Conjugués anticorps-médicament modifiés par une cystéine avec des lieurs contenant des peptides
US10647779B2 (en) 2009-04-29 2020-05-12 Bayer Intellectual Property Gmbh Anti-mesothelin immunoconjugates and uses therefor
WO2020113108A1 (fr) 2018-11-30 2020-06-04 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd38
WO2020117257A1 (fr) 2018-12-06 2020-06-11 Genentech, Inc. Thérapie combinée de lymphome diffus à grandes cellules b comprenant des immuno-conjugués anti-cd79b, un agent alkylant et un anticorps anti-cd20
EP3689910A2 (fr) 2014-09-23 2020-08-05 F. Hoffmann-La Roche AG Procédé d'utilisation d'immunoconjugués anti-cd79b
WO2020181164A1 (fr) 2019-03-06 2020-09-10 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer au moyen de récepteurs antigéniques chimériques automoteurs
WO2020191342A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps anti-claudine-6 et conjugués de médicaments
WO2020191344A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps de claudin-6 bispécifiques
US10787518B2 (en) 2016-06-14 2020-09-29 Xencor, Inc. Bispecific checkpoint inhibitor antibodies
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
WO2020205564A1 (fr) 2019-03-29 2020-10-08 Immunogen, Inc. Dérivés de bis-benzodiazépine cytotoxiques et leurs conjugués avec des agents de liaison à une cellule pour inhiber la croissance cellulaire anormale ou pour traiter des maladies prolifératives
WO2020219287A1 (fr) 2019-04-26 2020-10-29 Immunogen, Inc. Dérivés de camptothécine
WO2020216947A1 (fr) 2019-04-24 2020-10-29 Heidelberg Pharma Research Gmbh Conjugués anticorps-médicaments d'amatoxine et leurs utilisations
WO2020232169A1 (fr) 2019-05-14 2020-11-19 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome folliculaire
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
WO2020243546A1 (fr) 2019-05-30 2020-12-03 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-bcma
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
WO2020256544A1 (fr) 2019-06-17 2020-12-24 Tagworks Pharmaceuticals B.V. Tétrazines pour une vitesse et un rendement de libération de chimie clic élevés
WO2020256546A1 (fr) 2019-06-17 2020-12-24 Tagworks Pharmaceuticals B.V. Composés pour libération de chimie click rapide et efficace
WO2021003297A1 (fr) 2019-07-02 2021-01-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps monoclonaux se liant à egfrviii et leurs utilisations
US10898570B2 (en) 2015-07-07 2021-01-26 Genentech, Inc. Combination therapy with an anti-HER2 antibody-drug conjugate and a Bcl-2 inhibitor
EP3769787A1 (fr) 2015-06-29 2021-01-27 ImmunoGen, Inc. Conjugués d'anticorps à cystéine modifiée
EP3778602A1 (fr) 2015-07-21 2021-02-17 ImmunoGen, Inc. Procédés de préparation de dérivés de benzodiazépine cytotoxique
EP3778601A1 (fr) 2014-09-03 2021-02-17 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
US10925971B2 (en) 2016-11-29 2021-02-23 Regeneron Pharmaceuticals, Inc. Methods of treating PRLR positive breast cancer
EP3782654A1 (fr) 2014-09-12 2021-02-24 Genentech, Inc. Anticorps et immunoconjugués anti-her2
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
US10982006B2 (en) 2018-04-04 2021-04-20 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
WO2021076196A1 (fr) 2019-10-18 2021-04-22 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
WO2021097220A1 (fr) 2019-11-15 2021-05-20 Seagen Inc. Méthodes de traitement du cancer du sein her2 positif avec du tucatinib en combinaison avec un conjugué médicament-anticorps anti-her2
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
WO2021142199A1 (fr) 2020-01-09 2021-07-15 Mersana Therapeutics, Inc. Conjugués anticorps-médicament spécifiques à un site avec des lieurs contenant des peptides
US11084863B2 (en) 2017-06-30 2021-08-10 Xencor, Inc. Targeted heterodimeric Fc fusion proteins containing IL-15 IL-15alpha and antigen binding domains
WO2021173773A1 (fr) 2020-02-25 2021-09-02 Mediboston, Inc. Dérivés de camptothécine et leurs utilisations
EP3888691A1 (fr) 2016-11-14 2021-10-06 Hangzhou Dac Biotech Co., Ltd. Lieurs de conjugaison, conjugués médicament-molécule de liaison à une cellule contenant lesdits lieurs, procédés de préparation et d'utilisation de tels conjugués avec les lieurs
US11149088B2 (en) 2016-04-15 2021-10-19 Bioatla, Inc. Anti-Axl antibodies, antibody fragments and their immunoconjugates and uses thereof
WO2021217051A1 (fr) 2020-04-24 2021-10-28 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b
WO2021220199A1 (fr) 2020-04-30 2021-11-04 Novartis Ag Conjugués anticorps-médicament ccr7 pour le traitement du cancer
US11208632B2 (en) 2016-04-26 2021-12-28 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
WO2021262723A1 (fr) 2020-06-22 2021-12-30 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie tslpr-cd19 ou tslpr-cd22
WO2022010797A2 (fr) 2020-07-07 2022-01-13 Bionecure Therapeutics, Inc. Nouveaux maytansinoïdes en tant que charges utiles d'adc et leur utilisation pour le traitement du cancer
US11312770B2 (en) 2017-11-08 2022-04-26 Xencor, Inc. Bispecific and monospecific antibodies using novel anti-PD-1 sequences
US11319355B2 (en) 2017-12-19 2022-05-03 Xencor, Inc. Engineered IL-2 Fc fusion proteins
WO2022099026A1 (fr) 2020-11-05 2022-05-12 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd19/cd22
US11358999B2 (en) 2018-10-03 2022-06-14 Xencor, Inc. IL-12 heterodimeric Fc-fusion proteins
US11365258B2 (en) 2017-03-10 2022-06-21 Berlin-Chemie Ag Pharmaceutical combinations comprising an anti-LY75 antibody
WO2022180581A2 (fr) 2021-02-25 2022-09-01 Mediboston Limited Conjugués anticorps anti-her2-médicament et leurs utilisations
US11453711B2 (en) 2019-12-31 2022-09-27 Beijing Ql Biopharmaceutical Co., Ltd. Fusion proteins of GLP-1 and GDF15 and conjugates thereof
US11472890B2 (en) 2019-03-01 2022-10-18 Xencor, Inc. Heterodimeric antibodies that bind ENPP3 and CD3
WO2022241446A1 (fr) 2021-05-12 2022-11-17 Genentech, Inc. Méthodes d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
US11505595B2 (en) 2018-04-18 2022-11-22 Xencor, Inc. TIM-3 targeted heterodimeric fusion proteins containing IL-15/IL-15RA Fc-fusion proteins and TIM-3 antigen binding domains
US11510990B2 (en) 2020-01-11 2022-11-29 Beijing Ql Biopharmaceutical Co., Ltd. Conjugates of fusion proteins of GLP-1 and FGF21
US11524991B2 (en) 2018-04-18 2022-12-13 Xencor, Inc. PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof
US11529394B2 (en) 2020-09-30 2022-12-20 Beijing Ql Biopharmaceutical Co., Ltd. Polypeptide conjugates and methods of uses
WO2023019092A1 (fr) 2021-08-07 2023-02-16 Genentech, Inc. Méthodes d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
US11584927B2 (en) 2014-08-28 2023-02-21 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified T-cells
US11590169B1 (en) 2022-03-02 2023-02-28 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD123 immunotherapy
WO2023031445A2 (fr) 2021-09-06 2023-03-09 Veraxa Biotech Gmbh Nouveaux variants d'aminoacyl-arnt synthétase pour l'expansion de code génétique dans des eucaryotes
WO2023089314A1 (fr) 2021-11-18 2023-05-25 Oxford Biotherapeutics Limited Combinaisons pharmaceutiques
EP4186529A1 (fr) 2021-11-25 2023-05-31 Veraxa Biotech GmbH Conjugués anticorps-charge utile améliorés (apcs) préparés par conjugaison spécifique à un site à l'aide d'une expansion de code génétique
WO2023094525A1 (fr) 2021-11-25 2023-06-01 Veraxa Biotech Gmbh Conjugués anticorps-charge utile améliorés (apc) préparés par conjugaison spécifique à un site à l'aide d'une expansion de code génétique
WO2023104941A1 (fr) 2021-12-08 2023-06-15 European Molecular Biology Laboratory Charges utiles hydrophiles fonctionnalisées à la tétrazine destinées à la préparation de conjugués de ciblage
WO2023105248A1 (fr) 2021-12-11 2023-06-15 Cancer Research Technology Limited Immunothérapie pour le cancer
EP4218929A1 (fr) 2014-03-21 2023-08-02 AbbVie Inc. Anticorps anti-egfr et conjugués anticorps-médicament
WO2023158305A1 (fr) 2022-02-15 2023-08-24 Tagworks Pharmaceuticals B.V. Protéine il12 masquée
US11739144B2 (en) 2021-03-09 2023-08-29 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CLDN6
WO2023168243A1 (fr) 2022-03-02 2023-09-07 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd123
WO2023169896A1 (fr) 2022-03-09 2023-09-14 Astrazeneca Ab MOLÉCULES DE LIAISON DIRIGÉES CONTRE LE FRα
WO2023170216A1 (fr) 2022-03-11 2023-09-14 Astrazeneca Ab PROCÉDÉ DE NOTATION D'UNE THÉRAPIE PAR CONJUGUÉ ANTICORPS-MÉDICAMENTS ANTI-FRα
US11759527B2 (en) 2021-01-20 2023-09-19 Abbvie Inc. Anti-EGFR antibody-drug conjugates
US11859012B2 (en) 2021-03-10 2024-01-02 Xencor, Inc. Heterodimeric antibodies that bind CD3 and GPC3
WO2024013724A1 (fr) 2022-07-15 2024-01-18 Pheon Therapeutics Ltd Conjugués anticorps-médicament
WO2024023735A1 (fr) 2022-07-27 2024-02-01 Mediboston Limited Dérivés d'auristatine et conjugués de ceux-ci
WO2024026107A2 (fr) 2022-07-28 2024-02-01 Lentigen Technology, Inc. Thérapies par récepteur antigénique chimérique pour le traitement de tumeurs solides
WO2024044743A1 (fr) 2022-08-26 2024-02-29 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd20/cd19 entièrement humaine
US11919956B2 (en) 2020-05-14 2024-03-05 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3
WO2024080872A1 (fr) 2022-10-12 2024-04-18 Tagworks Pharmaceuticals B.V. Bicyclononènes contraints
US12006370B2 (en) 2018-07-23 2024-06-11 Heidelberg Pharma Research Gmbh Use of anti-CD5 antibody drug conjugate (ADC) in allogeneic cell therapy
WO2024121632A1 (fr) 2022-12-09 2024-06-13 Crispr Therapeutics Ag Utilisation d'un conjugué anticorps-médicament (adc) anti-cd117
US12029792B2 (en) 2018-12-04 2024-07-09 Der-Yang Tien Stereocomplexes for the delivery of anti-cancer agents
WO2024153789A1 (fr) 2023-01-20 2024-07-25 Basf Se Composition de biopolymère stabilisée, sa fabrication et son utilisation
WO2024170660A1 (fr) 2023-02-16 2024-08-22 Astrazeneca Ab Polythérapies pour le traitement du cancer avec des molécules de liaison thérapeutiques
WO2024191293A1 (fr) 2023-03-10 2024-09-19 Tagworks Pharmaceuticals B.V. Trans-cyclooctène à lieur t amélioré
US12129309B2 (en) 2022-05-04 2024-10-29 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE602004031239D1 (de) * 2003-07-21 2011-03-10 Immunogen Inc Verfahren zu dessen anwendung
NO347360B1 (no) * 2003-10-10 2023-09-25 Immunogen Inc Cellebindingsmiddelmaytansinoid-konjugat med formel trastuzumab-SMCC-DM1 eller trastuzumab-SIABDM1, fremgangsmåte for fremstilling av disse og en in vitro fremgangsmåte for å styre maytansinoider til en valgt cellepopulasjon eller for å eliminere celler, samt anvendelse.
SI2295073T1 (sl) * 2003-11-17 2014-07-31 Genentech, Inc. Protitelo proti CD22 za zdravljenje tumorja hematopoetskega izvora
CA2486285C (fr) * 2004-08-30 2017-03-07 Viktor S. Goldmakher Immunoconjugues ciblant des cellules a expression du syndecan-1 et utilisation de ceux-ci
NZ555601A (en) 2004-12-09 2009-07-31 Centocor Inc Anti-integrin immunoconjugates, methods and uses
EP1910557A2 (fr) 2005-04-07 2008-04-16 Chiron Corporation Genes associes au cancer
US20090214536A1 (en) 2005-04-07 2009-08-27 Guoying Yu CACNA1E in Cancer Diagnosis, Detection and Treatment
CA2647107A1 (fr) 2006-03-23 2007-09-27 Novartis Ag Therapeutique anticorps antigene de cellules anti-tumorales
KR20090010194A (ko) 2006-04-13 2009-01-29 노바티스 백신즈 앤드 다이아그노스틱스, 인크. 암의 치료, 진단 또는 검출 방법
EP2474556A3 (fr) 2007-03-14 2012-10-17 Novartis AG Inhibiteurs APCDD1 pour traiter, diagnostiquer ou détecter le cancer
PE20090481A1 (es) 2007-07-16 2009-05-18 Genentech Inc Anticuerpos anti-cd79b e inmunoconjugados humanizados y metodos de uso
CR20190516A (es) 2007-07-16 2020-02-18 Genentech Inc ANTICUERPOS ANTI-CD79B E INMUNOCONJUGADOS (Divisional 2015-0040)
MX2010007101A (es) * 2007-12-26 2011-07-01 Biotest Ag Metodos y agentes para mejorar el reconocimiento de celulas de tumor que expresan cd138.
PT2242772E (pt) * 2007-12-26 2015-02-09 Biotest Ag Imunoconjugados dirigidos contra cd138 e as suas utilizações
EP2238169A1 (fr) * 2007-12-26 2010-10-13 Biotest AG Procédé permettant de réduire les effets secondaires cytotoxiques et d'améliorer l'efficacité des immunoconjugués
DK2238168T3 (da) * 2007-12-26 2014-08-25 Biotest Ag Midler, der er målrettet mod cd138 og anvendelser deraf
CN101981055B (zh) 2008-01-31 2016-03-09 健泰科生物技术公司 抗cd79b抗体和免疫偶联物及使用方法
CA2757382A1 (fr) 2009-04-01 2010-10-21 Kristi Elkins Anticorps anti-fcrh5 et immunoconjugues
US20110076232A1 (en) * 2009-09-29 2011-03-31 Ludwig Institute For Cancer Research Specific binding proteins and uses thereof
PT2488873E (pt) 2009-10-16 2015-11-19 Novartis Ag Biomarcadores da resposta farmacodinâmica de tumores
CA2869704A1 (fr) * 2012-04-04 2013-10-10 Perseus Proteomics Inc. Conjugue d'anticorps anti-cdh3 anticorps (p-cadherine) et medicament
US9353150B2 (en) 2012-12-04 2016-05-31 Massachusetts Institute Of Technology Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment
CN104688740A (zh) * 2012-12-21 2015-06-10 百奥泰生物科技(广州)有限公司 类美登素衍生物及其制备方法和用途
EP2948478B1 (fr) 2013-01-25 2019-04-03 Amgen Inc. Anticorps ciblant cdh19 pour un mélanome
US10208125B2 (en) 2013-07-15 2019-02-19 University of Pittsburgh—of the Commonwealth System of Higher Education Anti-mucin 1 binding agents and uses thereof
CN110478495A (zh) 2014-06-30 2019-11-22 塔弗达治疗有限公司 靶向缀合物及其颗粒和制剂
US20190194315A1 (en) 2015-06-17 2019-06-27 Novartis Ag Antibody drug conjugates
WO2017197045A1 (fr) 2016-05-11 2017-11-16 Movassaghi Mohammad Synthèse totale convergente et énantiosélective d'analogues de la communesine
GB201615725D0 (en) * 2016-09-15 2016-11-02 Polytherics Ltd Novel cytotoxic agents and conjugates thereof
WO2018209239A1 (fr) 2017-05-11 2018-11-15 Massachusetts Institute Of Technology Dérivés d'agélastatine puissants en tant que modulateurs de l'invasion et de la métastase du cancer
US10640508B2 (en) 2017-10-13 2020-05-05 Massachusetts Institute Of Technology Diazene directed modular synthesis of compounds with quaternary carbon centers
EP3552631A1 (fr) 2018-04-10 2019-10-16 Inatherys Conjugués d'anticorps-médicament et leurs utilisations pour le traitement du cancer
EP3828206A4 (fr) 2018-07-25 2022-04-20 Daiichi Sankyo Company, Limited Procédé efficace de fabrication d'un conjugué anticorps-médicament
US20200046737A1 (en) 2018-08-09 2020-02-13 Notable Labs, Inc. Methods for treating cancer, and compositions therefor
US11535634B2 (en) 2019-06-05 2022-12-27 Massachusetts Institute Of Technology Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof
MX2023001962A (es) 2020-08-19 2023-04-26 Xencor Inc Composiciones anti-cd28.
US12030888B2 (en) 2021-02-24 2024-07-09 Massachusetts Institute Of Technology Himastatin derivatives, and processes of preparation thereof, and uses thereof
WO2023157989A1 (fr) 2022-02-17 2023-08-24 주식회사 노벨티노빌리티 Conjugué anticorps-médicament

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5208020A (en) * 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use

Family Cites Families (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3896111A (en) 1973-02-20 1975-07-22 Research Corp Ansa macrolides
US4151042A (en) 1977-03-31 1979-04-24 Takeda Chemical Industries, Ltd. Method for producing maytansinol and its derivatives
US4137230A (en) 1977-11-14 1979-01-30 Takeda Chemical Industries, Ltd. Method for the production of maytansinoids
US4265814A (en) 1978-03-24 1981-05-05 Takeda Chemical Industries Matansinol 3-n-hexadecanoate
US4307016A (en) 1978-03-24 1981-12-22 Takeda Chemical Industries, Ltd. Demethyl maytansinoids
JPS5562090A (en) 1978-10-27 1980-05-10 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164687A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
US4256746A (en) 1978-11-14 1981-03-17 Takeda Chemical Industries Dechloromaytansinoids, their pharmaceutical compositions and method of use
JPS5566585A (en) 1978-11-14 1980-05-20 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55102583A (en) 1979-01-31 1980-08-05 Takeda Chem Ind Ltd 20-acyloxy-20-demethylmaytansinoid compound
JPS55162791A (en) 1979-06-05 1980-12-18 Takeda Chem Ind Ltd Antibiotic c-15003pnd and its preparation
JPS55164685A (en) 1979-06-08 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164686A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
US4309428A (en) 1979-07-30 1982-01-05 Takeda Chemical Industries, Ltd. Maytansinoids
JPS5645483A (en) 1979-09-19 1981-04-25 Takeda Chem Ind Ltd C-15003phm and its preparation
JPS5645485A (en) 1979-09-21 1981-04-25 Takeda Chem Ind Ltd Production of c-15003pnd
EP0028683A1 (fr) 1979-09-21 1981-05-20 Takeda Chemical Industries, Ltd. Antibiotique C-15003 PHO et sa préparation
WO1982001188A1 (fr) 1980-10-08 1982-04-15 Takeda Chemical Industries Ltd Composes 4,5-deoxymaytansinoide et leur procede de preparation
US4450254A (en) 1980-11-03 1984-05-22 Standard Oil Company Impact improvement of high nitrile resins
US4313946A (en) 1981-01-27 1982-02-02 The United States Of America As Represented By The Secretary Of Agriculture Chemotherapeutically active maytansinoids from Trewia nudiflora
US4315929A (en) 1981-01-27 1982-02-16 The United States Of America As Represented By The Secretary Of Agriculture Method of controlling the European corn borer with trewiasine
JPS57192389A (en) 1981-05-20 1982-11-26 Takeda Chem Ind Ltd Novel maytansinoid
US4732863A (en) 1984-12-31 1988-03-22 University Of New Mexico PEG-modified antibody with reduced affinity for cell surface Fc receptors
US5010176A (en) 1988-11-10 1991-04-23 Eli Lilly And Company Antibody-drug conjugates
CA2006408A1 (fr) 1988-12-27 1990-06-27 Susumu Iwasa Anticorps monoclaux bispecifiques, production et utilisation
IL93733A (en) * 1989-04-14 1996-01-19 American Cyanamid Co History of Dissolved Drug Sulphides Antibacterial and Antibacterial, Prepared from Compounds Containing Methyl-Thriteo Groups and Their Target Form
CA2026147C (fr) * 1989-10-25 2006-02-07 Ravi J. Chari Agents cytotoxiques comprenant des maytansinoides et leur usage therapeutique
US6316003B1 (en) * 1989-12-21 2001-11-13 Whitehead Institute For Biomedical Research Tat-derived transport polypeptides
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
GB9120467D0 (en) * 1991-09-26 1991-11-06 Celltech Ltd Anti-hmfg antibodies and process for their production
ES2313867T3 (es) 1991-12-02 2009-03-16 Medical Research Council Produccion de anticuerpos anti-auto de repertorios de segmentos de anticuerpo expresados en la superficie de fagos.
ATE210464T1 (de) * 1992-06-09 2001-12-15 Neorx Corp BIOTIN-DOTA KONJUGATE UND DEREN VERWENDUNG IN ßPRETARGETINGß VERFAHREN
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5612474A (en) * 1994-06-30 1997-03-18 Eli Lilly And Company Acid labile immunoconjugate intermediates
WO1999006587A2 (fr) 1997-08-01 1999-02-11 Morphosys Ag Nouvelle methode et nouveau phage d'identification d'une sequence d'acide nucleique
ES2466715T3 (es) 1999-06-25 2014-06-11 Immunogen, Inc. Métodos de tratamiento usando conjugados de anticuerpo anti-ErbB-maitansinoide
EP1235618A2 (fr) 1999-09-07 2002-09-04 Conjuchem, Inc. Diffusion pulmonaire permettant la bioconjugaison
CA2385528C (fr) * 1999-10-01 2013-12-10 Immunogen, Inc. Compositions et methodes de traitement du cancer utilisant des immunoconjugues et des agents chimiotherapeutiques
US6333410B1 (en) * 2000-08-18 2001-12-25 Immunogen, Inc. Process for the preparation and purification of thiol-containing maytansinoids
EP1258255A1 (fr) * 2001-05-18 2002-11-20 Boehringer Ingelheim International GmbH Conjugués d'un anticorps contre CD44 et d'un maytansinoide
US6441163B1 (en) * 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US6716821B2 (en) * 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
WO2003057163A2 (fr) * 2002-01-03 2003-07-17 Smithkline Beecham Corporation Preparation d'immunoconjugues

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5208020A (en) * 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use

Cited By (650)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE43899E1 (en) 1999-10-01 2013-01-01 Immunogen Inc. Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
USRE44704E1 (en) 1999-10-01 2014-01-14 Immunogen Inc. Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
US20100136033A1 (en) * 2000-03-16 2010-06-03 Immunogen, Inc. METHODS OF TREATMENT USING ANTI-ErbB ANTIBODY-MAYTANSINOID CONJUGATES
US8337856B2 (en) 2000-03-16 2012-12-25 Immunogen, Inc. Methods of treatment using anti-ERBB antibody-maytansinoid conjugates
USRE39151E1 (en) 2000-08-18 2006-06-27 Immunogen, Inc. Process for the preparation and purification of thiol-containing maytansinoids
US20040014980A1 (en) * 2000-09-12 2004-01-22 Smithkline Beecham Plc Process and intermediates
US6884874B2 (en) * 2000-09-12 2005-04-26 Smithkline Beecham Corporation Process and intermediates
US20040072997A1 (en) * 2000-12-20 2004-04-15 Alsobrook John P. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20050113571A1 (en) * 2001-03-16 2005-05-26 Smithkline Beecham Corporation Process for preparing maytansinol
US9562102B2 (en) 2001-05-11 2017-02-07 Ludwig Institute For Cancer Research Specific binding proteins and uses thereof
US20030055226A1 (en) * 2001-05-31 2003-03-20 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US7368565B2 (en) * 2001-05-31 2008-05-06 Immunogen Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US20030138425A1 (en) * 2001-09-21 2003-07-24 Mather Jennie Powell Antibodies that bind to cancer-associated antigen cytokeratin 8 and methods of use thereof
US7744878B2 (en) 2001-10-16 2010-06-29 Raven Biotechnologies, Inc. Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
US20070128202A1 (en) * 2001-10-16 2007-06-07 Mather Jennie P Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
US7148038B2 (en) 2001-10-16 2006-12-12 Raven Biotechnologies, Inc. Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
US20030108966A1 (en) * 2001-10-16 2003-06-12 Mather Jennie P. Antibodies that bind to cancer-associated antigen CD46 and methods of use thereof
US20110045005A1 (en) * 2001-10-19 2011-02-24 Craig Crowley Compositions and methods for the treatment of tumor of hematopoietic origin
US20040048312A1 (en) * 2002-04-12 2004-03-11 Ronghao Li Antibodies that bind to integrin alpha-v-beta-6 and methods of use thereof
US20040048319A1 (en) * 2002-05-03 2004-03-11 Mather Jennie P. ALCAM and ALCAM modulators
US8779098B2 (en) 2002-06-19 2014-07-15 Macrogenics West, Inc. B7-H3L cell surface antigen and antibodies that bind thereto
US9574007B2 (en) 2002-06-19 2017-02-21 Macrogenics, Inc. B7-H3L cell surface antigen and antibodies that bind thereto
US20040037833A1 (en) * 2002-06-19 2004-02-26 Mather Jennie P. Novel RAAG10 cell surface target and a family of antibodies recognizing that target
EP2277917A2 (fr) 2002-06-19 2011-01-26 Raven Biotechnologies, Inc. Cible de surface B7-H3L et famille d'anticorps reconnaissant cette cible
US7527969B2 (en) 2002-06-19 2009-05-05 Raven Biotechnologies, Inc. RAAG10 cell surface target and a family of antibodies recognizing that target
US20090202561A1 (en) * 2002-06-19 2009-08-13 Mather Jennie P Novel raag10 cell surface target and a family of antibodies recognizing that target
US6913748B2 (en) * 2002-08-16 2005-07-05 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
WO2004016801A3 (fr) * 2002-08-16 2004-07-01 Immunogen Inc Agents de reticulation a reactivite et solubilite elevees et utilisation de ceux-ci dans la preparation de conjugues pour l'administration ciblee de medicaments a petites molecules
AU2003259163B2 (en) * 2002-08-16 2008-07-03 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
US20040039176A1 (en) * 2002-08-16 2004-02-26 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
WO2004016801A2 (fr) * 2002-08-16 2004-02-26 Immunogen, Inc. Agents de reticulation a reactivite et solubilite elevees et utilisation de ceux-ci dans la preparation de conjugues pour l'administration ciblee de medicaments a petites molecules
EP2298806A1 (fr) 2002-10-16 2011-03-23 Purdue Pharma L.P. Anticorps se fixant sur des polypeptides CA 125/0722P associés à des cellules et leurs procédés d'utilisation
EP3301114A1 (fr) 2002-10-16 2018-04-04 Purdue Pharma LP Polypeptides de fusion d'anticorps se fixant sur des polypeptides ca 125/o722p associés a des cellules
EP2891666A1 (fr) 2002-10-16 2015-07-08 Purdue Pharma L.P. Anticorps se fixant sur des polypeptides CA 125/O722P associes a des cellules et leurs procedes d'utilisation
US20040171814A1 (en) * 2002-11-13 2004-09-02 Mather Jennie P. Antigen PIPA and antibodies that bind thereto
US7405061B2 (en) 2002-11-13 2008-07-29 Raven Biotechnologies, Inc. Antigen PIPA and antibodies that bind thereto
US9085630B2 (en) 2002-11-15 2015-07-21 Genentech, Inc. Compositions and methods for the treatment of tumor of hematopoietic origin
EP3000886A1 (fr) 2003-03-19 2016-03-30 Amgen Fremont Inc. Anticorps contre l'antigene de lymphocytes t, du domaine d'immunoglobuline et du domaine 1 de mucine (tim-1) et leurs utilisations
WO2004084823A2 (fr) 2003-03-19 2004-10-07 Abgenix, Inc. Anticorps contre l'antigene de lymphocytes t, du domaine d'immunoglobuline et du domaine 1 de mucine (tim-1) et leurs utilisations
US7432088B2 (en) 2003-05-08 2008-10-07 Immunogen Inc. Methods for the production of ansamitocins
US20050170475A1 (en) * 2003-05-08 2005-08-04 Immunogen Methods for the production of ansamitocins
EP2281577A2 (fr) 2003-05-14 2011-02-09 Immunogen, Inc. Composition constituée de conjuges de médicaments
US20040241174A1 (en) * 2003-05-14 2004-12-02 Immunogen, Inc. Drug conjugate composition
US7501120B2 (en) 2003-05-14 2009-03-10 Immunogen, Inc. Drug conjugate composition
US20070009541A1 (en) * 2003-05-14 2007-01-11 Immunogen, Inc. Drug conjugate composition
US20070009540A1 (en) * 2003-05-14 2007-01-11 Immunogen, Inc. Drug conjugate composition
US20070009539A1 (en) * 2003-05-14 2007-01-11 Immunogen, Inc. Drug conjugate composition
US20090142361A1 (en) * 2003-05-14 2009-06-04 Immunogen, Inc. Drug conjugate composition
US8012485B2 (en) 2003-05-14 2011-09-06 Immunogen, Inc. Drug conjugate composition
US7514080B2 (en) 2003-05-14 2009-04-07 Immunogen, Inc. Drug conjugate composition
US7494649B2 (en) 2003-05-14 2009-02-24 Immunogen, Inc. Drug conjugate composition
US7374762B2 (en) 2003-05-14 2008-05-20 Immunogen, Inc. Drug conjugate composition
KR101145506B1 (ko) 2003-05-20 2012-05-15 이뮤노젠 아이엔씨 새로운 메이탠시노이드를 포함하는 개선된 세포독성체
EA010909B1 (ru) * 2003-05-20 2008-12-30 Иммьюноджен, Инк. Усовершенствованные цитотоксические агенты, содержащие новые мэйтансиноиды
US20070270585A1 (en) * 2003-05-20 2007-11-22 Immunogen, Inc. Cytotoxic agents comprising new maytansinoids
CN101186613A (zh) * 2003-05-20 2008-05-28 伊缪诺金公司 含有新的美登素类的改进的细胞毒剂
US20110158991A1 (en) * 2003-05-20 2011-06-30 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
CN101186613B (zh) * 2003-05-20 2014-09-17 伊缪诺金公司 含有新的美登素类的改进的细胞毒剂
US7851432B2 (en) 2003-05-20 2010-12-14 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
US8435528B2 (en) 2003-05-20 2013-05-07 Immunogen, Inc. Cytotoxic agents comprising new maytansinoids
US8841425B2 (en) 2003-05-20 2014-09-23 Immunogen, Inc. Cytotoxic agents comprising new maytansinoids
US7473796B2 (en) * 2003-05-20 2009-01-06 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
WO2004103272A3 (fr) * 2003-05-20 2006-11-23 Immunogen Inc Agents cytotoxiques ameliores contenant de nouveaux maytansinoides
US20050031617A1 (en) * 2003-06-06 2005-02-10 Jing Ma Antibodies specific for cancer associated antigen SM5-1 and uses thereof
US20050232926A1 (en) * 2003-06-06 2005-10-20 Oncomax Acquisition Corp. Antibodies specific for cancer associated antigen SM5-1 and uses thereof
US9096672B2 (en) 2003-06-27 2015-08-04 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
EP3011971A1 (fr) 2003-06-27 2016-04-27 Amgen Fremont Inc. Anticorps dirigés vers les mutants de suppression de récepteur de facteur de croissance épidermique et utilisations associées
EP2457587A1 (fr) 2003-06-27 2012-05-30 Amgen Fremont Inc. Anticorps dirigés vers les mutants de suppression de récepteur de facteur de croissance épidermique et utilisations associées
EP2457586A1 (fr) 2003-06-27 2012-05-30 Amgen Fremont Inc. Anticorps dirigés vers les mutants de suppression de récepteur de facteur de croissance épidermique et utilisations associées
US20050053608A1 (en) * 2003-06-27 2005-03-10 Richard Weber Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
EP3037105A1 (fr) 2003-06-27 2016-06-29 Amgen Fremont Inc. Anticorps dirigés vers les mutants de suppression de récepteur de facteur de croissance épidermique et utilisations associées
US10118968B2 (en) 2003-06-27 2018-11-06 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20050059087A1 (en) * 2003-06-27 2005-03-17 Richard Weber Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US9062113B2 (en) 2003-06-27 2015-06-23 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US9085624B2 (en) 2003-06-27 2015-07-21 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US7736644B2 (en) 2003-06-27 2010-06-15 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US7628986B2 (en) 2003-06-27 2009-12-08 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20090240038A1 (en) * 2003-06-27 2009-09-24 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US11492411B2 (en) 2003-06-27 2022-11-08 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20090155282A1 (en) * 2003-06-27 2009-06-18 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20090156790A1 (en) * 2003-06-27 2009-06-18 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20090175887A1 (en) * 2003-06-27 2009-07-09 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US9073998B2 (en) 2003-06-27 2015-07-07 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US20100111979A1 (en) * 2003-06-27 2010-05-06 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
EP3679951A1 (fr) 2003-06-27 2020-07-15 Amgen Fremont Inc. Anticorps dirigés vers les mutants de suppression de récepteur de facteur de croissance épidermique et utilisations associées
US10508153B2 (en) 2003-06-27 2019-12-17 Amgen Fremont Inc. Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
US8987424B2 (en) 2003-07-21 2015-03-24 Immunogen, Inc. CA6 antigen-specific cytotoxic conjugate and methods of using the same
US9370584B2 (en) 2003-07-21 2016-06-21 Immunogen Inc. CA6 antigen-specific cytotoxic conjugate and methods of using the same
US20090099336A1 (en) * 2003-07-21 2009-04-16 Immunogen Inc. CA6 Antigen-Specific Cytotoxic Conjugate and Methods of Using the Same
US20110064733A1 (en) * 2003-07-21 2011-03-17 Immunogen, Inc. Ca6 antigen-specific cytotoxic conjugate and methods of using the same
US9822183B2 (en) 2003-07-21 2017-11-21 Sanofi CA6 antigen-specific cytotoxic conjugate and methods of using the same
US20050152907A1 (en) * 2003-09-18 2005-07-14 Liang Tony W. KID3 and KID3 antibodies that bind thereto
US20100322851A1 (en) * 2003-09-18 2010-12-23 Macrogenics, Inc. KID3 and KID3 Antibodies That Bind Thereto
US7790855B2 (en) 2003-09-18 2010-09-07 Macrogenics, Inc. KID3 and KID3 antibodies that bind thereto
US8440197B2 (en) 2003-09-18 2013-05-14 Macrogenics, Inc. KID3 and KID3 antibodies that bind thereto
WO2005028498A2 (fr) 2003-09-18 2005-03-31 Raven Biotechnologies, Inc. Kid3 et anticorps de liaison a kid3
US8563509B2 (en) 2003-10-10 2013-10-22 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
WO2005037992A2 (fr) 2003-10-10 2005-04-28 Immunogen, Inc. Procede de ciblage de populations cellulaires specifiques a l'aide de conjugues formes d'un agent de liaison cellulaire et de maytansinoides, lies par l'intermediaire d'un lieur non clivable, lesdits conjugues et leurs procedes de preparation
US7989598B2 (en) 2003-10-10 2011-08-02 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
US20080114153A1 (en) * 2003-10-10 2008-05-15 Immunogen. Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
US20050169933A1 (en) * 2003-10-10 2005-08-04 Immunogen, Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US8685920B2 (en) 2003-10-10 2014-04-01 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
EP2596803A3 (fr) * 2003-10-10 2013-09-11 ImmunoGen, Inc. Procédé de ciblage de populations de cellules spécifiques au moyen de conjugués de maytansinoïdes avec des agents se liant aux cellules, liés par une liaison non clivable, lesdits conjugués et procédés de fabrication desdits conjugués
US20080171865A1 (en) * 2003-10-10 2008-07-17 Immunogen, Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
US20080171856A1 (en) * 2003-10-10 2008-07-17 Immunogen, Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
US8163888B2 (en) * 2003-10-10 2012-04-24 Immunogen, Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US10844135B2 (en) 2003-10-10 2020-11-24 Immunogen, Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said
EP2612682A2 (fr) 2003-10-10 2013-07-10 ImmunoGen, Inc. Procédé de ciblage de populations de cellules spécifiques au moyen de conjugués maytansinoïdes d'agents de liaison cellulaire liés par un lien non clivable, lesdits conjugués et procédés de fabrication desdits conjugués
US8198417B2 (en) 2003-10-10 2012-06-12 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
EP2596804A2 (fr) 2003-10-10 2013-05-29 ImmunoGen, Inc. Procédé de ciblage de populations de cellules spécifiques au moyen de conjugués de maytansinoïdes avec des agents se liant aux cellules, liés par une liaison non clivable, lesdits conjugués et procédés de fabrication desdits conjugués
EP2596803A2 (fr) 2003-10-10 2013-05-29 ImmunoGen, Inc. Procédé de ciblage de populations de cellules spécifiques au moyen de conjugués de maytansinoïdes avec des agents se liant aux cellules, liés par une liaison non clivable, lesdits conjugués et procédés de fabrication desdits conjugués
CN107198778A (zh) * 2003-10-10 2017-09-26 伊缪诺金公司 用经不可切割接头连接的细胞结合剂美登木素生物碱偶联物
WO2005044998A2 (fr) 2003-11-05 2005-05-19 Palingen, Inc. Cytotoxicite augmentee de l'anticorps de liaison cdim contre les lymphocytes b
US20050112130A1 (en) * 2003-11-05 2005-05-26 Bhat Neelima M. Enhanced B cell cytotoxicity of CDIM binding antibody
EP2332992A1 (fr) 2004-03-23 2011-06-15 Biogen Idec MA Inc. Agents de couplage de récepteur et leurs utilisations thérapeutiques
US20050276812A1 (en) * 2004-06-01 2005-12-15 Genentech, Inc. Antibody-drug conjugates and methods
US8142784B2 (en) 2004-06-01 2012-03-27 Genentech, Inc. Antibody-drug conjugates and methods
EP2286844A2 (fr) 2004-06-01 2011-02-23 Genentech, Inc. Conjugués anticorps-médicament et procédés
US8652479B2 (en) 2004-06-01 2014-02-18 Genentech, Inc. Antibody-drug conjugates and methods
US20080171040A1 (en) * 2004-06-01 2008-07-17 Genentech, Inc. Antibody-drug conjugates and methods
US20090202536A1 (en) * 2004-06-01 2009-08-13 Genentech, Inc. Antibody-drug conjugates and methods
US7572895B2 (en) 2004-06-07 2009-08-11 Raven Biotechnologies, Inc. Transferrin receptor antibodies
US20060039908A1 (en) * 2004-06-07 2006-02-23 Mather Jennie P Transferrin receptor antibodies
US20090181039A1 (en) * 2004-06-15 2009-07-16 Bristol-Myers Squibb Company Conjugates with reduced adverse systemic effects
US20050287155A1 (en) * 2004-06-15 2005-12-29 Santi Daniel V Conjugates with reduced adverse systemic effects
US7541330B2 (en) 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
EP3088004A1 (fr) 2004-09-23 2016-11-02 Genentech, Inc. Anticorps et conjugués modifiés au niveau des cystéines
US9458241B2 (en) 2004-11-05 2016-10-04 Igm Biosciences, Inc. Antibody induced cell membrane wounding
EP2305716A2 (fr) 2004-11-30 2011-04-06 Curagen Corporation Anticorps diriges contre la gpnmb et leurs utilisations
EP2842571A1 (fr) 2004-11-30 2015-03-04 Celldex Therapeutics, Inc. Anticorps diriges contre la GPNMB et leurs utilisations
EP2311880A2 (fr) 2005-01-05 2011-04-20 Biogen Idec MA Inc. Molécules à crypto-liaison
EP2311881A2 (fr) 2005-01-05 2011-04-20 Biogen Idec MA Inc. Molécules à crypto-liaison
US7687242B2 (en) 2005-01-12 2010-03-30 Raven Biotechnologies, Inc. KID31 and antibodies that bind thereto
US20060166291A1 (en) * 2005-01-12 2006-07-27 Mather Jennie P KID31 and antibodies that bind thereto
US8313916B2 (en) 2005-01-12 2012-11-20 Macrogenics West, Inc. KID31 and antibodies that bind thereto
EP2514828A2 (fr) 2005-01-19 2012-10-24 ImmunoGen, Inc. Procédés de production d'ansamitocine
WO2006078368A1 (fr) * 2005-01-19 2006-07-27 Immunogen, Inc. Procedes de production d'ansamitocines
CN104745655A (zh) * 2005-01-19 2015-07-01 伊缪诺金公司 用于制备安丝菌素的方法
EA012524B1 (ru) * 2005-01-19 2009-10-30 Иммьюноджен, Инк. Способы производства ансамитоцинов
US20110045006A1 (en) * 2005-01-31 2011-02-24 Macrogenics West, Inc. LUCA2 and Antibodies That Bind Thereto
US7847070B2 (en) 2005-01-31 2010-12-07 Raven Biotechnologies, Inc. LUCA2 and antibodies that bind thereto
US20060172349A1 (en) * 2005-01-31 2006-08-03 Mather Jennie P LUCA2 and antibodies that bind thereto
US8361475B2 (en) 2005-02-02 2013-01-29 Macrogenics West, Inc. ADAM-9 modulators
US7674619B2 (en) 2005-02-02 2010-03-09 Mather Jennie P ADAM-9 modulators
US20060171952A1 (en) * 2005-02-02 2006-08-03 Mather Jennie P JAM-3 and antibodies that bind thereto
US20060172350A1 (en) * 2005-02-02 2006-08-03 Mather Jennie P ADAM-9 modulators
US20090269340A1 (en) * 2005-02-03 2009-10-29 Mather Jennie P Antibodies to oncostatin m receptor
US7572896B2 (en) 2005-02-03 2009-08-11 Raven Biotechnologies, Inc. Antibodies to oncostatin M receptor
US8216578B2 (en) 2005-02-03 2012-07-10 Macrogenics, Inc. Antibodies to oncostatin M receptor
WO2006084226A2 (fr) 2005-02-04 2006-08-10 Raven Biotechnologies, Inc. Anticorps se liant a epha2 et procedes d'utilisation de ceux-ci
US7569672B2 (en) 2005-02-04 2009-08-04 Raven Biotechnologies, Inc. Antibodies that bind to EphA2 and methods of use thereof
US20060177453A1 (en) * 2005-02-04 2006-08-10 Mather Jennie P Antibodies that bind to EphA2 and methods of use thereof
US20100086969A1 (en) * 2005-02-04 2010-04-08 Macrogenics, Inc. Antibodies That Bind to EphA2 and Methods of Use Thereof
US8183357B2 (en) 2005-02-04 2012-05-22 Macrogenics, Inc. Antibodies that bind to EphA2 and methods of use thereof
US20060182750A1 (en) * 2005-02-11 2006-08-17 Immunogen, Inc. Process for preparing stable drug conjugates
WO2006086733A2 (fr) 2005-02-11 2006-08-17 Immunogen, Inc. Procede pour preparer des conjugues medicamenteux stables
US20110166319A1 (en) * 2005-02-11 2011-07-07 Immunogen, Inc. Process for preparing purified drug conjugates
EP2468304A2 (fr) 2005-02-11 2012-06-27 ImmunoGen, Inc. Procédé de préparation de conjugués de médicaments stables
EP2384767A1 (fr) 2005-03-24 2011-11-09 Millennium Pharmaceuticals, Inc. Anticorps se liant à l'OV064 et leurs procédés d'utilisation
WO2006113623A3 (fr) * 2005-04-15 2008-09-12 Immunogen Inc Elimination d'une population de cellules heterogenes ou mixtes dans des tumeurs
US20090076263A1 (en) * 2005-04-15 2009-03-19 Immunogen Inc. Elimination of heterogeneous or mixed cell population in tumors
US8388960B2 (en) 2005-04-15 2013-03-05 Immunogen Inc. Elimination of heterogeneous or mixed cell population in tumors
CN101374545B (zh) * 2005-04-15 2012-03-28 免疫基因公司 消除肿瘤中的异质或混合细胞群体
US8137669B2 (en) 2005-04-15 2012-03-20 Immunogen, Inc. Elimination of heterogeneous or mixed cell population in tumors
US20060233814A1 (en) * 2005-04-15 2006-10-19 Immunogen Inc. Elimination of heterogeneous or mixed cell population in tumors
USRE47223E1 (en) 2005-06-20 2019-02-05 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US9114179B2 (en) 2005-08-03 2015-08-25 Immunogen, Inc. Immunoconjugate formulations
US20070031402A1 (en) * 2005-08-03 2007-02-08 Immunogen Inc. Immunoconjugate formulations
US11471536B2 (en) 2005-08-24 2022-10-18 Immunogen, Inc. Process for preparing purified drug conjugates
US7811572B2 (en) 2005-08-24 2010-10-12 Immunogen, Inc. Process for preparing purified drug conjugates
US8933205B2 (en) 2005-08-24 2015-01-13 Immunogen, Inc. Process for preparing purified drug conjugates
EP2662096A1 (fr) 2005-08-24 2013-11-13 ImmunoGen, Inc. Procédé de préparation de conjugués d'anticorps de maytansinoïde
US20110021744A1 (en) * 2005-08-24 2011-01-27 Immunogen, Inc. Process for preparing purified drug conjugates
US9789204B2 (en) 2005-08-24 2017-10-17 Immunogen, Inc. Process for preparing purified drug conjugates
US20070048314A1 (en) * 2005-08-24 2007-03-01 Immunogen, Inc. Process for preparing purified drug conjugates
EP3539572A1 (fr) 2005-08-24 2019-09-18 ImmunoGen, Inc. Procédé de préparation de conjugués d'anticorps de maytansinoïde
EP2399609A1 (fr) 2005-08-24 2011-12-28 ImmunoGen, Inc. Procédé de préparation de conjugués d'anticorps et de maytansinoïde
US8383122B2 (en) 2005-08-24 2013-02-26 Immunogen, Inc. Process for preparing purified drug conjugates
CN102989000B (zh) * 2005-08-24 2016-04-20 伊缪诺金公司 制备美登木素生物碱抗体缀合物的方法
EP2548583A2 (fr) 2005-11-10 2013-01-23 Curagen Corporation Methode de traitement du cancer de l'ovaire et du rein utilisant des anticorps diriges contre l'antigene a domaine 1 de mucine et a domaine immunoglobuline des lymphocytes t (tim-1)
EP1806365A1 (fr) 2006-01-05 2007-07-11 Boehringer Ingelheim International GmbH Anticorps spécifiques pour la protéine alpha d'activation de fibroblastes et leurs immunoconjugués
EP2446904A2 (fr) 2006-05-30 2012-05-02 Genentech, Inc. Anti-CD22 anticorps, immuno-conjugués et utilisations associées
US8394607B2 (en) 2006-05-30 2013-03-12 Genentech, Inc. Anti-CD22 antibodies and immunoconjugates and methods of use
US8524865B2 (en) 2006-05-30 2013-09-03 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
US20080050310A1 (en) * 2006-05-30 2008-02-28 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
US8226945B2 (en) 2006-05-30 2012-07-24 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
US20110142859A1 (en) * 2006-05-30 2011-06-16 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
EP2447282A2 (fr) 2006-05-30 2012-05-02 Genentech, Inc. Anti-CD22 Anticorps, immuno-conjugués et utilisations associées
US8968741B2 (en) 2006-05-30 2015-03-03 Genentech, Inc. Anti-CD22 antibodies and immunoconjugates and methods of use
US8460667B2 (en) 2006-07-18 2013-06-11 Sanofi EPHA2 receptor antagonist antibodies
USRE47123E1 (en) 2006-07-18 2018-11-13 Sanofi EPHA2 receptor antagonist antibodies
US20100047257A1 (en) * 2006-07-18 2010-02-25 Sanofi-Aventis Antagonist antibody for the treatment of cancer
EP3909980A1 (fr) 2006-10-19 2021-11-17 Sanofi Nouveaux anticorps anti-cd38 pour le traitement du cancer
EP3498735A1 (fr) 2006-10-19 2019-06-19 Sanofi Anticorps anti-cd38 pour le traitement de la leucemie
EP2845866A1 (fr) 2006-10-27 2015-03-11 Genentech, Inc. Anticorps et immuno-conjugués et utilisations associées
WO2008066691A2 (fr) 2006-11-08 2008-06-05 Macrogenics West, Inc. Tes7, et anticorps se liant à celui-ci
US9090693B2 (en) 2007-01-25 2015-07-28 Dana-Farber Cancer Institute Use of anti-EGFR antibodies in treatment of EGFR mutant mediated disease
US9023356B2 (en) 2007-03-15 2015-05-05 Ludwig Institute For Cancer Research Ltd Treatment method using EGFR antibodies and SRC inhibitors and related formulations
US10214580B2 (en) 2007-03-27 2019-02-26 I2 Pharmaceuticals, Inc. Constructs and libraries comprising antibody surrogate light chain sequences
USRE47194E1 (en) 2007-05-08 2019-01-08 Genentech, Inc. Cysteine engineered anti-MUC16 antibodies and antibody drug conjugates
US20090011060A1 (en) * 2007-07-06 2009-01-08 Peter Koepke Campsiandra angustifolia extract and methods of extracting and using such extract
US20090017140A1 (en) * 2007-07-09 2009-01-15 Peter Koepke Maytenus abenfolia extract and methods of extracting and using such extract
US20090035395A1 (en) * 2007-08-01 2009-02-05 Peter Koepke Spondias mombin l. extract and methods of extracting and using such extract
EP2562187A1 (fr) 2007-08-09 2013-02-27 Boehringer Ingelheim International GmbH Anticorps anti-CD37
EP2241577A1 (fr) 2007-08-09 2010-10-20 Boehringer Ingelheim International GmbH Anticorps anti-CD37
US9283276B2 (en) 2007-08-14 2016-03-15 Ludwig Institute For Cancer Research Ltd. Monoclonal antibody 175 targeting the EGF receptor and derivatives and uses thereof
US20090074891A1 (en) * 2007-09-18 2009-03-19 Peter Koepke Combretum laurifolium mart. extract and methods of extracting and using such extract
US7879369B2 (en) 2007-09-18 2011-02-01 Selvamedica, Llc Combretum laurifolium Mart. extract and methods of extracting and using such extract
EP3692988A2 (fr) 2008-03-18 2020-08-12 Genentech, Inc. Combinaisons d'un conjugué de médicament-anticorps anti-her2 et 5-fu, anticorps anti-vegf, carboplatin ou abt869 et procédés d'utilisation
US8663643B2 (en) 2008-03-18 2014-03-04 Genentech, Inc. Combinations of an anti-HER2 antibody-drug conjugate and chemotherapeutic agents, and methods of use
EP2638907A2 (fr) 2008-03-18 2013-09-18 Genentech, Inc. Combinaisons de conjugué de médicament-anticorps anti-HER2 et du lapatinib
EP2644194A2 (fr) 2008-03-18 2013-10-02 Genentech, Inc. Combinaisons de conjugué de médicament-anticorps anti-HER2 et de docétaxel
EP2644204A2 (fr) 2008-03-18 2013-10-02 Genentech, Inc. Combinaisons de conjugué de médicament-anticorps anti-HER2 et du pertuzumab
EP3269366A2 (fr) 2008-03-18 2018-01-17 Genentech, Inc. Combinaisons d'un conjugué de médicament-anticorps anti-her2 et lapatinib et procédés d'utilisation
US9150649B2 (en) 2008-04-30 2015-10-06 Immunogen, Inc. Potent conjugates and hydrophilic linkers
EP3266469A2 (fr) 2008-04-30 2018-01-10 ImmunoGen, Inc. Agents de réticulation et leurs utilisations
US20100129314A1 (en) * 2008-04-30 2010-05-27 Immunogen Inc. Potent conjugates and hydrophilic linkers
WO2010091150A1 (fr) 2009-02-05 2010-08-12 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
EP3360879A1 (fr) 2009-02-05 2018-08-15 ImmunoGen, Inc. Dérivés de benzodiazépine en tant qu'agents cytotoxiques
EP3100745A1 (fr) 2009-02-05 2016-12-07 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
US9879249B2 (en) 2009-02-17 2018-01-30 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
US9238878B2 (en) 2009-02-17 2016-01-19 Redwood Bioscience, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
US9072798B2 (en) 2009-02-18 2015-07-07 Ludwig Institute For Cancer Research Ltd. Specific binding proteins and uses thereof
US10647779B2 (en) 2009-04-29 2020-05-12 Bayer Intellectual Property Gmbh Anti-mesothelin immunoconjugates and uses therefor
US10781263B2 (en) 2009-04-29 2020-09-22 Bayer Intellectual Property Gmbh Anti-mesothelin immunoconjugates and uses therefor
WO2010126551A1 (fr) 2009-04-30 2010-11-04 Immunogen, Inc. Conjugués puissants et séquences de liaison hydrophiles
US10017561B2 (en) 2009-05-13 2018-07-10 I2 Pharmaceuticals, Inc. Neutralizing molecules to influenza viruses
EP3480202A1 (fr) 2009-06-03 2019-05-08 ImmunoGen, Inc. Procédés de conjugaison
AU2017201214B2 (en) * 2009-06-03 2019-09-05 Immunogen, Inc. Conjugation methods
US9376500B2 (en) 2009-06-03 2016-06-28 Immunogen, Inc. Conjugation methods
US10233257B2 (en) 2009-06-03 2019-03-19 Immunogen, Inc. Methods for preparing antibody-drug conjugates
AU2015201534B2 (en) * 2009-06-03 2016-11-24 Immunogen, Inc. Conjugation methods
US8624003B2 (en) * 2009-06-03 2014-01-07 Immunogen, Inc. Methods for preparation of antibody-maytansinoid conjugates
US10815309B2 (en) * 2009-06-03 2020-10-27 Immunogen, Inc. Methods for preparing antibody-drug conjugates
WO2010141566A1 (fr) 2009-06-03 2010-12-09 Immunogen, Inc. Procédés de conjugaison
US20110003969A1 (en) * 2009-06-03 2011-01-06 Immunogen Inc. Conjugation methods
US20230105468A1 (en) * 2009-06-03 2023-04-06 Immunogen, Inc. Conjugation methods
US9771432B2 (en) 2009-06-03 2017-09-26 Immunogen, Inc. Conjugation methods
US11498979B2 (en) * 2009-06-03 2022-11-15 Immunogen, Inc. Methods for preparing a purified maytansinoid conjugate in a solution
EP3248619A2 (fr) 2009-06-04 2017-11-29 Novartis AG Procédés d'identification de sites de conjugaison igg
WO2010141902A2 (fr) 2009-06-04 2010-12-09 Novartis Ag Procédés d'identification de sites pour la conjugaison d'igg
EP2896404A2 (fr) 2009-06-04 2015-07-22 Novartis AG Procédés d'identification de sites de conjugaison IgG
US9676856B2 (en) 2009-08-13 2017-06-13 The Johns Hopkins University Methods of modulating immune function
US8840889B2 (en) 2009-08-13 2014-09-23 The Johns Hopkins University Methods of modulating immune function
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
US9676864B2 (en) 2009-10-02 2017-06-13 Sanofi Antibodies that specifically bind to the EphA2 receptor
WO2011039724A1 (fr) 2009-10-02 2011-04-07 Sanofi-Aventis Anticorps qui se lient spécifiquement au récepteur epha2
US8668910B2 (en) 2009-10-02 2014-03-11 Sanofi Antibodies that specifically bind to the EphA2 receptor
EP3520816A2 (fr) 2009-10-23 2019-08-07 Millennium Pharmaceuticals, Inc. Molécules d'anticorps anti-gcc et compositions et procédés associés
US10941211B2 (en) 2009-10-23 2021-03-09 Millennium Pharmaceuticals, Inc. Anti-GCC antibody molecules and related compositions and methods
US10584181B2 (en) 2009-12-04 2020-03-10 Genentech, Inc. Methods of making and using multispecific antibody panels and antibody analog panels
EP3778917A2 (fr) 2009-12-04 2021-02-17 F. Hoffmann-La Roche AG Anticorps multispécifiques, analogues d'anticorps, compositions et procédés
WO2011069074A2 (fr) 2009-12-04 2011-06-09 Genentech, Inc. Procédés de traitement de cancer du sein métastasique avec trastuzumab-mcc-dm1
WO2011100403A1 (fr) 2010-02-10 2011-08-18 Immunogen, Inc Anticorps anti-cd20 et utilisations de ceux-ci
EP3196212A1 (fr) 2010-02-24 2017-07-26 Immunogen, Inc. Anticorps de récepteur 1 de folate et immunoconjugués et leurs utilisations
WO2011109400A2 (fr) 2010-03-04 2011-09-09 Macrogenics,Inc. Anticorps réagissant avec b7-h3, fragments immunologiquement actifs associés et utilisations associées
EP2982380A1 (fr) 2010-03-04 2016-02-10 MacroGenics, Inc. Anticorps réagissant avec b7-h3, fragments immunologiquement actifs associés et utilisations associées
EP3620467A1 (fr) 2010-03-12 2020-03-11 Debiopharm International SA Molécules de liaison cd37 et immunoconjugués correspondants
US8771966B2 (en) 2010-06-03 2014-07-08 Genentech, Inc. Immuno-PET imaging of antibodies and immunoconjugates and uses therefor
WO2011153346A1 (fr) 2010-06-03 2011-12-08 Genentech, Inc. Imagerie par immuno-tep d'anticorps et d'immunoconjugués et utilisations correspondantes
WO2011156328A1 (fr) 2010-06-08 2011-12-15 Genentech, Inc. Anticorps et conjugués modifiés par la cystéine
WO2012016227A2 (fr) 2010-07-29 2012-02-02 Xencor, Inc. Anticorps dont les points isoélectriques sont modifiés
EP3029066A2 (fr) 2010-07-29 2016-06-08 Xencor, Inc. Anticorps à points isoélectriques modifiés
US9605061B2 (en) 2010-07-29 2017-03-28 Xencor, Inc. Antibodies with modified isoelectric points
US8637641B2 (en) 2010-07-29 2014-01-28 Xencor, Inc. Antibodies with modified isoelectric points
WO2012019024A2 (fr) 2010-08-04 2012-02-09 Immunogen, Inc. Molécules se liant à her3 et leurs immunoconjugués
WO2012047724A1 (fr) 2010-09-29 2012-04-12 Agensys, Inc. Conjugués anticorps-médicaments (adc) se liant aux protéines 191p4d12
EP3409287A1 (fr) 2010-09-29 2018-12-05 Agensys, Inc. Conjugués anticorps-médicaments (adc) se liant aux protéines 191p4d12
EP3903812A1 (fr) 2010-09-29 2021-11-03 Agensys, Inc. Conjugués anticorps-médicaments (adc) se liant aux protéines 191p4d12
EP3219731A1 (fr) 2010-10-01 2017-09-20 Oxford BioTherapeutics Ltd Anticorps anti-ror1
EP3828205A1 (fr) 2010-10-01 2021-06-02 Oxford BioTherapeutics Ltd Anticorps anti-ror1
WO2012045085A1 (fr) 2010-10-01 2012-04-05 Oxford Biotherapeutics Ltd. Anticorps anti-ror1
US9125896B2 (en) 2010-10-29 2015-09-08 Immunogen, Inc. EGFR-binding molecules and immunoconjugates thereof
US8790649B2 (en) 2010-10-29 2014-07-29 Immunogen, Inc. EGFR-binding molecules and immunoconjugates thereof
US9238690B2 (en) 2010-10-29 2016-01-19 Immunogen, Inc. Non-antagonistic EGFR-binding molecules and immunoconjugates thereof
US9309322B2 (en) 2010-11-12 2016-04-12 Scott & White Healthcare (Swh) Antibodies to tumor endothelial marker 8
US10273299B2 (en) 2010-11-12 2019-04-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Antibodies to tumor endothelial marker 8
WO2012065161A2 (fr) 2010-11-12 2012-05-18 Scott & White Healthcare Anticorps contre le marqueur 8 endothélial tumoral
WO2012074757A1 (fr) 2010-11-17 2012-06-07 Genentech, Inc. Conjugués d'anticorps alaninyl-maytansinol
WO2012078771A1 (fr) 2010-12-09 2012-06-14 Genentech, Inc. Traitement de cancer her2-positif avec du paclitaxel et du trastuzumab-mcc-dm1
EP3284755A1 (fr) 2010-12-30 2018-02-21 Takeda Pharmaceutical Company Limited Anticorps anti-cd38 conjugués
WO2012092616A1 (fr) 2010-12-30 2012-07-05 Takeda Pharmaceutical Company Limited Anticorps anti-cd38 conjugués
EP3798231A1 (fr) 2010-12-30 2021-03-31 Takeda Pharmaceutical Company Limited Anticorps anti-cd38 conjugués
WO2012092539A2 (fr) 2010-12-31 2012-07-05 Takeda Pharmaceutical Company Limited Anticorps contre dll4 et leurs utilisations
US9540438B2 (en) 2011-01-14 2017-01-10 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US10183998B2 (en) 2011-01-14 2019-01-22 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof
US10570211B2 (en) 2011-01-24 2020-02-25 Gilead Sciences, Inc. Antibodies selective for cells presenting EGFR at high density
US12084510B2 (en) 2011-01-24 2024-09-10 Gilead Sciences, Inc. Antibodies selective for cells presenting EGFR at high density
WO2012109624A2 (fr) 2011-02-11 2012-08-16 Zyngenia, Inc. Complexes plurispécifiques monovalents et multivalents et leurs utilisations
EP3498303A1 (fr) 2011-02-15 2019-06-19 ImmunoGen, Inc. Procédés de préparation de conjugués
EP3053600A1 (fr) 2011-02-15 2016-08-10 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
WO2012128868A1 (fr) 2011-02-15 2012-09-27 Immunogen, Inc. Dérivés cytotoxiques de benzodiazépine
WO2012112687A1 (fr) 2011-02-15 2012-08-23 Immunogen, Inc. Procédés de préparation de conjugués
WO2012112708A1 (fr) 2011-02-15 2012-08-23 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et procédés de préparation
EP3666289A1 (fr) 2011-02-15 2020-06-17 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
US8795673B2 (en) * 2011-03-29 2014-08-05 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US11090390B2 (en) 2011-03-29 2021-08-17 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US11744900B2 (en) 2011-03-29 2023-09-05 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US9914748B2 (en) 2011-03-29 2018-03-13 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US9428543B2 (en) 2011-03-29 2016-08-30 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US20120253021A1 (en) * 2011-03-29 2012-10-04 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
US10435432B2 (en) 2011-03-29 2019-10-08 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
EP3492494A1 (fr) 2011-05-21 2019-06-05 MacroGenics, Inc. Molécules de liaison cd3 capables de se lier à des anticorps cd3 humains et non humains
WO2012162067A2 (fr) 2011-05-21 2012-11-29 Macrogenics, Inc. Molécules de liaison des cd3 capables de se lier aux cd3 humaines et non humaines
WO2012162561A2 (fr) 2011-05-24 2012-11-29 Zyngenia, Inc. Complexes plurispécifiques multivalents et monovalents, et leurs utilisations
EP3228325A1 (fr) 2011-06-10 2017-10-11 Mersana Therapeutics, Inc. Conjugués protéine-polymère-médicament
WO2012171020A1 (fr) 2011-06-10 2012-12-13 Mersana Therapeutics, Inc. Conjugués de médicament-protéine-polymère
WO2012177837A2 (fr) 2011-06-21 2012-12-27 Immunogen, Inc. Nouveaux dérivés de maytansinoïde comprenant un lieur peptidique et conjugués correspondants
WO2013012733A1 (fr) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Régions fc hétérodimères, molécules de liaison les comprenant, et méthodes associées
US10300140B2 (en) 2011-07-28 2019-05-28 I2 Pharmaceuticals, Inc. Sur-binding proteins against ERBB3
WO2013022855A1 (fr) 2011-08-05 2013-02-14 Xencor, Inc. Anticorps avec points isoélectriques modifiés et immunofiltration
WO2013033380A1 (fr) 2011-08-31 2013-03-07 Genentech, Inc. Marqueurs de diagnostic
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
EP3611187A1 (fr) 2011-10-10 2020-02-19 Xencor, Inc. Procédé de purification d'anticorps
WO2013055809A1 (fr) 2011-10-10 2013-04-18 Xencor, Inc. Procédé de purification d'anticorps
WO2013063001A1 (fr) 2011-10-28 2013-05-02 Genentech, Inc. Associations thérapeutiques et méthodes de traitement du mélanome
WO2013075048A1 (fr) 2011-11-16 2013-05-23 Amgen Inc. Procédé de traitement de troubles associés au mutant de délétion viii du récepteur du facteur de croissance épidermique
US9233171B2 (en) 2011-11-21 2016-01-12 Immunogen, Inc. Method of treatment of tumors that are resistant to EGFR antibody therapies by EGFR antibody cytotoxic agent conjugate
WO2013083817A1 (fr) 2011-12-08 2013-06-13 Biotest Ag Utilisations d'immunoconjugués ciblant cd138
US9975956B2 (en) 2011-12-22 2018-05-22 I2 Pharmaceuticals, Inc. Surrogate binding proteins which bind DR4 and/or DR5
WO2013106489A1 (fr) 2012-01-09 2013-07-18 The Scripps Research Institute Anticorps humanisés à cdr3 ultralongues
EP3663314A1 (fr) 2012-01-09 2020-06-10 The Scripps Research Institute Anticorps humanisés avec cdr3s ultralong
WO2013106485A2 (fr) 2012-01-09 2013-07-18 The Scripps Research Institute Régions déterminant la complémentarité ultralongues et utilisations associées
WO2013109994A1 (fr) 2012-01-20 2013-07-25 Sea Lane Biotechnologies, Llc Conjugués surrobody
US9409976B2 (en) 2012-02-08 2016-08-09 Igm Biosciences, Inc. CDIM binding proteins and uses thereof
WO2013130093A1 (fr) 2012-03-02 2013-09-06 Genentech, Inc. Biomarqueurs pour un traitement à base de composés chimiothérapeutiques anti-tubuline
US9175089B2 (en) 2012-03-30 2015-11-03 Genentech, Inc. Anti-LGR5 antibodies and immunoconjugates
WO2013149159A1 (fr) 2012-03-30 2013-10-03 Genentech, Inc. Anticorps et immunoconjugués anti-lgr5
WO2013160396A1 (fr) 2012-04-26 2013-10-31 Boehringer Ingelheim International Gmbh Combinaison d'anticorps cd37 avec la bendamustine
WO2013165940A1 (fr) 2012-05-01 2013-11-07 Genentech, Inc. Anticorps anti-pmel17 et immunoconjugués
US9056910B2 (en) 2012-05-01 2015-06-16 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
US9597411B2 (en) 2012-05-01 2017-03-21 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
US10196454B2 (en) 2012-05-01 2019-02-05 Genentech, Inc. Anti-PMEL17 antibodies and immunoconjugates
WO2013171287A1 (fr) 2012-05-16 2013-11-21 Boehringer Ingelheim International Gmbh Combinaison d'anticorps anti-cd37 avec ice (ifosmamide, carboplatine, etoposide)
WO2013171289A1 (fr) 2012-05-16 2013-11-21 Boehringer Ingelheim International Gmbh Combinaison d'anticorps anti-cd37 avec d'autres agents
EP3545968A1 (fr) 2012-06-08 2019-10-02 F. Hoffmann-La Roche AG Sélectivité mutante et combinaisons d'un composé inhibiteur de phosphoinositide kinase 3 et d'agents chimiothérapeutiques pour le traitement du cancer
WO2013182668A1 (fr) 2012-06-08 2013-12-12 F. Hoffmann-La Roche Ag Sélectivité mutante et associations d'un inhibiteur de phospho‑inositide 3 kinase et agents chimiothérapeutiques pour le traitement du cancer
EP3494996A1 (fr) 2012-08-23 2019-06-12 Agensys, Inc. Conjugués anticorps-médicament (adc) qui se lient aux protéines 158p1d7
EP3904358A1 (fr) 2012-09-26 2021-11-03 ImmunoGen, Inc. Procédés améliorés d'acylation de maytansinol
EP3486248A1 (fr) 2012-09-26 2019-05-22 ImmunoGen, Inc. Procédés améliorés d'acylation de maytansinol
US10035817B2 (en) 2012-10-04 2018-07-31 Immunogen, Inc. Method of purifying cell-binding agent-cytotoxic agent conjugates with a PVDF membrane
WO2014055877A1 (fr) 2012-10-04 2014-04-10 Immunogen, Inc. Utilisation d'une membrane de pvdf pour purifier des conjugués d'agent de liaison cellulaire-agent cytotoxique
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
WO2014089335A2 (fr) 2012-12-07 2014-06-12 Amgen Inc. Protéines de liaison à l'antigène bcma
WO2014093379A1 (fr) 2012-12-10 2014-06-19 Mersana Therapeutics, Inc. Composés auristatine et leurs conjugués
US10226535B2 (en) 2012-12-10 2019-03-12 Mersana Therapeutics, Inc. Auristatin compounds and conjugates thereof
WO2014093394A1 (fr) 2012-12-10 2014-06-19 Mersana Therapeutics, Inc. Conjugués protéine-polymère-médicament
WO2014093640A1 (fr) 2012-12-12 2014-06-19 Mersana Therapeutics,Inc. Conjugués hydroxy-polymère-médicament-protéine
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
US9650446B2 (en) 2013-01-14 2017-05-16 Xencor, Inc. Heterodimeric proteins
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US10738132B2 (en) 2013-01-14 2020-08-11 Xencor, Inc. Heterodimeric proteins
US10472427B2 (en) 2013-01-14 2019-11-12 Xencor, Inc. Heterodimeric proteins
US10738133B2 (en) 2013-01-14 2020-08-11 Xencor, Inc. Heterodimeric proteins
US11634506B2 (en) 2013-01-14 2023-04-25 Xencor, Inc. Heterodimeric proteins
US11718667B2 (en) 2013-01-14 2023-08-08 Xencor, Inc. Optimized antibody variable regions
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
WO2014113510A1 (fr) 2013-01-15 2014-07-24 Xencor, Inc. Elimination rapide de complexes antigéniques à l'aide de nouveaux anticorps
US9738722B2 (en) 2013-01-15 2017-08-22 Xencor, Inc. Rapid clearance of antigen complexes using novel antibodies
WO2014134483A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014134486A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
EP3566750A2 (fr) 2013-02-28 2019-11-13 ImmunoGen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
WO2014160160A2 (fr) 2013-03-13 2014-10-02 Novartis Ag Conjugués anticorps-médicaments
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
WO2014159835A1 (fr) 2013-03-14 2014-10-02 Genentech, Inc. Anticorps et immunoconjugués anti-b7-h4
US10150813B2 (en) 2013-03-14 2018-12-11 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
US11230600B2 (en) 2013-03-14 2022-01-25 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
EP3299391A1 (fr) 2013-03-14 2018-03-28 Genentech, Inc. Anticorps et immunoconjugués anti-b7-h4
US10544187B2 (en) 2013-03-15 2020-01-28 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
EP3424530A1 (fr) 2013-03-15 2019-01-09 Zyngenia, Inc. Complexes multispécifiques monovalents et multivalents et leurs utilisations
US11814423B2 (en) 2013-03-15 2023-11-14 Xencor, Inc. Heterodimeric proteins
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
WO2014145090A1 (fr) 2013-03-15 2014-09-18 Regeneron Pharmaceuticals, Inc. Molécules biologiquement actives, leurs conjugués, et utilisations thérapeutiques
WO2014144466A1 (fr) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anticorps anti-alpha ν bêta 6 et leurs utilisations
EP3587448A1 (fr) 2013-03-15 2020-01-01 Xencor, Inc. Protéines hétérodimériques
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
WO2014143739A2 (fr) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anticorps anti-alpha ν bêta 6 et leurs utilisations
EP3514178A1 (fr) 2013-03-15 2019-07-24 Novartis AG Conjugués anticorps-médicament
US10287364B2 (en) 2013-03-15 2019-05-14 Xencor, Inc. Heterodimeric proteins
US10117953B2 (en) 2013-03-15 2018-11-06 Novartis Ag Antibody drug conjugates
US9498543B2 (en) 2013-03-15 2016-11-22 Novartis Ag Antibody drug conjugates
EP3936521A1 (fr) 2013-03-15 2022-01-12 Xencor, Inc. Protéines hétérodimériques
US11299554B2 (en) 2013-03-15 2022-04-12 Xencor, Inc. Heterodimeric proteins
EP3964237A1 (fr) 2013-03-15 2022-03-09 Regeneron Pharmaceuticals, Inc. Molécules biologiquement actives, leurs conjugués, et utilisations thérapeutiques
EP3421495A2 (fr) 2013-03-15 2019-01-02 Xencor, Inc. Modulation de cellules t avec des anticorps bispécifiques et des fusions fc
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
US9789203B2 (en) 2013-03-15 2017-10-17 Novartis Ag cKIT antibody drug conjugates
WO2014145806A2 (fr) 2013-03-15 2014-09-18 Xencor, Inc. Protéines hétérodimériques
WO2014182970A1 (fr) 2013-05-08 2014-11-13 Zymeworks Inc. Constructions de liaison aux antigènes her2 et her3 bispécifiques
WO2014194030A2 (fr) 2013-05-31 2014-12-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
US9518017B2 (en) 2013-06-28 2016-12-13 Immunogen, Inc. Purification of intermediates used in the preparation of heterobifunctional linkers
WO2014210267A1 (fr) * 2013-06-28 2014-12-31 Immunogen, Inc. Purification d'intermédiaires utilisés pour préparer des lieurs hétérobifonctionnels
WO2015000062A1 (fr) 2013-07-05 2015-01-08 Avidbiologics Inc. Conjugués d'anticorps anti-egfr
WO2015010100A2 (fr) 2013-07-18 2015-01-22 Fabrus, Inc. Anticorps humanisés comprenant des régions déterminant la complémentarité ultralongues
WO2015017146A2 (fr) 2013-07-18 2015-02-05 Fabrus, Inc. Anticorps à régions de détermination de complémentarité ultralongues
WO2015017552A1 (fr) 2013-08-01 2015-02-05 Agensys, Inc. Conjugués anticorps-médicament (adc) se liant à la protéine cd37
US11633500B2 (en) 2013-08-01 2023-04-25 Agensys, Inc. Antibody drug conjugates (ADC) that bind to CD37 proteins
US10646583B2 (en) 2013-08-01 2020-05-12 Agensys, Inc. Antibody drug conjugates (ADC) that bind to CD37 proteins
US9925273B2 (en) 2013-08-01 2018-03-27 Agensys, Inc. Antibody drug conjugates (ADC) that bind to CD37 proteins
US9688764B2 (en) 2013-08-21 2017-06-27 Regeneron Pharmaceuticals, Inc. Methods of treating breast cancer by administering anti-human prolactin receptor (PRLR) antibodies
US9545451B2 (en) 2013-08-21 2017-01-17 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
US9302015B2 (en) 2013-08-21 2016-04-05 Regeneron Pharmaceuticals, Inc. Anti-PRLR antibodies and methods for killing PRLR-expressing cells
US10683354B2 (en) 2013-08-21 2020-06-16 Regeneron Pharmaceuticals, Inc. Antibody-drug conjugates comprising anti-prolactin receptor (PRLR) antibodies and methods of use thereof to kill PRLR-expressing cells
US10106616B2 (en) 2013-08-21 2018-10-23 Regeneron Pharmaceuticals, Inc. Antagonist antibodies to human prolactin receptor (PRLR)
US10246515B2 (en) 2013-09-17 2019-04-02 Genentech, Inc. Methods of treating hedgehog-related diseases with an anti-LGR5 antibody
WO2015042108A1 (fr) 2013-09-17 2015-03-26 Genentech, Inc. Procédés d'utilisation d'anticorps anti-lgr5
WO2015054400A2 (fr) 2013-10-08 2015-04-16 Immunogen, Inc. Schémas posologiques d'immunoconjugués anti-folr1
EP3653228A1 (fr) 2013-10-08 2020-05-20 ImmunoGen, Inc. Schémas posologiques d'immunoconjugués anti-folr1
EP4424323A2 (fr) 2013-10-08 2024-09-04 ImmunoGen, Inc. Schémas posologiques d'immunoconjugués anti-folr1
US11434278B2 (en) 2013-10-11 2022-09-06 Asana Biosciences, Llc Protein-polymer-drug conjugates
WO2015054659A1 (fr) 2013-10-11 2015-04-16 Mersana Therapeutics, Inc. Conjugués de médicament-protéine-polymère
WO2015052537A1 (fr) 2013-10-11 2015-04-16 Oxford Biotherapeutics Ltd Anticorps conjugué contre ly75 pour le traitement du cancer
EP4269421A2 (fr) 2013-10-11 2023-11-01 The United States of America, as represented by The Secretary, Department of Health and Human Services Anticorps tem8 et leur utilisation
WO2015054669A1 (fr) 2013-10-11 2015-04-16 Asana Biosciences, Llc Conjugués médicament-polymère-protéine
US10316080B2 (en) 2013-10-11 2019-06-11 Asana Biosciences, Llc Protein-polymer-drug conjugates
EP3620470A1 (fr) 2013-10-11 2020-03-11 The United States of America, as represented by The Secretary, Department of Health and Human Services Anticorps tem8 et leur utilisation
WO2015069922A2 (fr) 2013-11-06 2015-05-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps anti-alk, conjugues, et recepteurs antigeniques chimeriques, et leur utilisation
WO2015073721A1 (fr) 2013-11-13 2015-05-21 Zymeworks Inc. Produits de recombinaison liant un antigène monovalent et ciblant l'egfr et/ou l'her2 et leurs utilisations
WO2015089344A1 (fr) 2013-12-13 2015-06-18 Genentech, Inc. Anticorps et immunoconjugués anti-cd33
EP3461845A1 (fr) 2013-12-13 2019-04-03 Genentech, Inc. Anticorps et immunoconjugués anti-cd33
WO2015095227A2 (fr) 2013-12-16 2015-06-25 Genentech, Inc. Composés peptidomimétiques et conjugués anticorps-médicament de ceux-ci
WO2015094900A1 (fr) 2013-12-18 2015-06-25 Imclone Llc Composés contre le récepteur 3 du facteur de croissance des fibroblastes (fgfr3) et utilisations thérapeutiques
US9375488B2 (en) 2013-12-18 2016-06-28 ImClone, LLC Compounds to fibroblast growth factor receptor-3 (FGFR3) and methods of treatment
US9943606B2 (en) 2014-01-15 2018-04-17 Rutgers, The State University Of New Jersey Dendritic polypeptide-based nanocarriers for the delivery of therapeutic agents
WO2015112909A1 (fr) 2014-01-24 2015-07-30 Genentech, Inc. Procédés d'utilisation d'anticorps anti-steap1 et immunoconjugués
US10100115B2 (en) 2014-02-14 2018-10-16 Macrogenics, Inc. Methods for the treatment of vascularizing cancers
WO2015127685A1 (fr) 2014-02-28 2015-09-03 Hangzhou Dac Biotech Co., Ltd Lieurs chargés et leurs utilisations pour la conjugaison
US10696700B2 (en) 2014-02-28 2020-06-30 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
US10683314B2 (en) 2014-02-28 2020-06-16 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
US10696699B2 (en) 2014-02-28 2020-06-30 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
US10464955B2 (en) 2014-02-28 2019-11-05 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
EP4218929A1 (fr) 2014-03-21 2023-08-02 AbbVie Inc. Anticorps anti-egfr et conjugués anticorps-médicament
US10858451B2 (en) 2014-03-28 2020-12-08 Xencor, Inc. Bispecific antibodies that bind to CD38 and CD3
EP3699195A2 (fr) 2014-03-28 2020-08-26 Xencor, Inc. Anticorps bispécifiques se liant à cd38 et cd3
US9822186B2 (en) 2014-03-28 2017-11-21 Xencor, Inc. Bispecific antibodies that bind to CD38 and CD3
US11840579B2 (en) 2014-03-28 2023-12-12 Xencor, Inc. Bispecific antibodies that bind to CD38 and CD3
EP3954713A2 (fr) 2014-03-28 2022-02-16 Xencor, Inc. Anticorps bispécifiques se liant à cd38 et cd3
WO2015149077A1 (fr) 2014-03-28 2015-10-01 Xencor, Inc. Anticorps bispécifiques se liant à cd38 et cd3
WO2015164665A1 (fr) 2014-04-25 2015-10-29 Genentech, Inc. Méthodes de traitement du cancer du sein précoce avec du trastuzumab-mcc-dm1 et du pertuzumab
WO2015179658A2 (fr) 2014-05-22 2015-11-26 Genentech, Inc. Immunoconjugués et anticorps anti-gpc3
WO2016001485A1 (fr) 2014-06-30 2016-01-07 Glykos Finland Oy Dérivé de saccharide d'une charge utile toxique et conjugués d'anticorps de celui-ci
EP3682904A1 (fr) 2014-06-30 2020-07-22 Glykos Finland Oy Dérivé de saccharide d'une charge utile toxique et conjugués d'anticorps de celui-ci
US10973920B2 (en) 2014-06-30 2021-04-13 Glykos Finland Oy Saccharide derivative of a toxic payload and antibody conjugates thereof
WO2016014984A1 (fr) 2014-07-24 2016-01-28 Xencor, Inc. Élimination rapide de complexes antigéniques à l'aide de nouveaux anticorps
WO2016024195A1 (fr) 2014-08-12 2016-02-18 Novartis Ag Conjugués médicament-anticorps anti-cdh6
US11584927B2 (en) 2014-08-28 2023-02-21 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified T-cells
US10603388B2 (en) 2014-09-02 2020-03-31 Immunogen, Inc. Methods for formulating antibody drug conjugate compositions
EP3311846A1 (fr) 2014-09-02 2018-04-25 ImmunoGen, Inc. Procédés de formulation de compositions de conjugués anticorps-médicament
EP3778601A1 (fr) 2014-09-03 2021-02-17 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
WO2016036804A1 (fr) 2014-09-03 2016-03-10 Immunogen, Inc. Dérivés de benzodiazépine cytotoxique
WO2016040868A1 (fr) 2014-09-12 2016-03-17 Genentech, Inc. Anticorps anti-cll-1 et immunoconjugués
EP3782654A1 (fr) 2014-09-12 2021-02-24 Genentech, Inc. Anticorps et immunoconjugués anti-her2
US11286302B2 (en) 2014-09-12 2022-03-29 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
EP3693391A1 (fr) 2014-09-12 2020-08-12 Genentech, Inc. Anticorps et immunoconjugués anti-cll-1
US10059768B2 (en) 2014-09-12 2018-08-28 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
WO2016040856A2 (fr) 2014-09-12 2016-03-17 Genentech, Inc. Anticorps et conjugués modifiés génétiquement avec de la cystéine
WO2016044396A1 (fr) 2014-09-17 2016-03-24 Genentech, Inc. Immunoconjugués comprenant des anticorps anti-her2 et des pyrrolobenzodiazépines
EP3689910A2 (fr) 2014-09-23 2020-08-05 F. Hoffmann-La Roche AG Procédé d'utilisation d'immunoconjugués anti-cd79b
WO2016075670A1 (fr) 2014-11-14 2016-05-19 Novartis Ag Conjugués anticorps-médicament
US10913803B2 (en) 2014-11-26 2021-02-09 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US11673972B2 (en) 2014-11-26 2023-06-13 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US9850320B2 (en) 2014-11-26 2017-12-26 Xencor, Inc. Heterodimeric antibodies to CD3 X CD20
US11111315B2 (en) 2014-11-26 2021-09-07 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US11859011B2 (en) 2014-11-26 2024-01-02 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US11352442B2 (en) 2014-11-26 2022-06-07 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38
US11225528B2 (en) 2014-11-26 2022-01-18 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US11945880B2 (en) 2014-11-26 2024-04-02 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
US10526417B2 (en) 2014-11-26 2020-01-07 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38
US9856327B2 (en) 2014-11-26 2018-01-02 Xencor, Inc. Heterodimeric antibodies to CD3 X CD123
US10889653B2 (en) 2014-11-26 2021-01-12 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
EP3903826A1 (fr) 2014-12-04 2021-11-03 Celgene Corporation Conjugués de biomolécules
EP4289483A2 (fr) 2014-12-04 2023-12-13 Celgene Corporation Conjugués de biomolécules
WO2016090157A1 (fr) 2014-12-04 2016-06-09 Celgene Corporation Conjugués de biomolécule
US10428155B2 (en) 2014-12-22 2019-10-01 Xencor, Inc. Trispecific antibodies
US11091548B2 (en) 2015-03-05 2021-08-17 Xencor, Inc. Modulation of T cells with bispecific antibodies and Fc fusions
US10227411B2 (en) 2015-03-05 2019-03-12 Xencor, Inc. Modulation of T cells with bispecific antibodies and FC fusions
WO2016141387A1 (fr) 2015-03-05 2016-09-09 Xencor, Inc. Modulation de lymphocytes t avec des anticorps bispécifiques et des hybrides fc
WO2016145099A1 (fr) 2015-03-09 2016-09-15 Agensys, Inc. Conjugués anticorps-médicament (cam) se liant aux protéines flt3
WO2016196373A2 (fr) 2015-05-30 2016-12-08 Genentech, Inc. Procédés de traitement de cancer du sein métastatique her2 positif
US11406715B2 (en) 2015-05-30 2022-08-09 Genentech, Inc. Methods of treating HER2-positive metastatic breast cancer
WO2016196285A1 (fr) 2015-06-04 2016-12-08 Imclone Llc Thérapies utilisant des composés qui ciblent le récepteur 3 du facteur de croissance des fibroblastes (fgfr3)
WO2016200676A1 (fr) 2015-06-08 2016-12-15 Immunogen, Inc. Combinaisons d'immunoconjugués anti-cd37 et d'anticorps anti-cd20
WO2016201394A1 (fr) 2015-06-12 2016-12-15 Miltenyi Biotec Technology, Inc. Procédé de traitement de cancer à l'aide de lymphocytes t génétiquement modifiés
EP3845557A1 (fr) 2015-06-12 2021-07-07 Lentigen Technology, Inc. Procédé de traitement de cancer à l'aide de lymphocytes t génétiquement modifiés
EP4286511A2 (fr) 2015-06-12 2023-12-06 Lentigen Technology, Inc. Procédé de traitement de cancer à l'aide de lymphocytes t génétiquement modifiés
US10639329B2 (en) 2015-06-12 2020-05-05 Lentigen Technology, Inc. Method to treat cancer with engineered T-cells
EP3769787A1 (fr) 2015-06-29 2021-01-27 ImmunoGen, Inc. Conjugués d'anticorps à cystéine modifiée
US10898570B2 (en) 2015-07-07 2021-01-26 Genentech, Inc. Combination therapy with an anti-HER2 antibody-drug conjugate and a Bcl-2 inhibitor
WO2015151081A2 (fr) 2015-07-12 2015-10-08 Suzhou M-Conj Biotech Co., Ltd Lieurs de pontage pour la conjugaison d'une molécule de liaison cellulaire
US10293055B2 (en) 2015-07-15 2019-05-21 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10328157B2 (en) 2015-07-15 2019-06-25 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
US10232051B2 (en) 2015-07-15 2019-03-19 Hangzhou Dac Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
EP3778602A1 (fr) 2015-07-21 2021-02-17 ImmunoGen, Inc. Procédés de préparation de dérivés de benzodiazépine cytotoxique
EP4286387A2 (fr) 2015-07-21 2023-12-06 ImmunoGen, Inc. Procédés de préparation de dérivés de benzodiazépine cytotoxique
US10509035B2 (en) 2015-08-07 2019-12-17 Gamamabs Pharma Sa Antibodies, antibody drug conjugates and methods of use
US10172875B2 (en) 2015-09-17 2019-01-08 Immunogen, Inc. Therapeutic combinations comprising anti-FOLR1 immunoconjugates
US11033564B2 (en) 2015-09-17 2021-06-15 Immunogen, Inc. Therapeutic combinations comprising anti-FOLR1 immunoconjugates
WO2017049149A1 (fr) 2015-09-17 2017-03-23 Immunogen, Inc. Combinaisons thérapeutiques comprenant des immunoconjugués anti-folr1
WO2017062952A1 (fr) 2015-10-09 2017-04-13 Miltenyi Biotec Technology, Inc. Récepteurs antigéniques chimériques et leurs procédés d'utilisation
EP3660044A1 (fr) 2015-10-09 2020-06-03 Miltenyi Biotec Technology, Inc. Récepteur d'antigène chimérique et ses utilisations
US10729738B2 (en) 2015-10-16 2020-08-04 Genentech, Inc. Hindered disulfide drug conjugates
WO2017064675A1 (fr) 2015-10-16 2017-04-20 Genentech, Inc. Conjugués médicamenteux à pont disulfure encombré
WO2017087280A1 (fr) 2015-11-16 2017-05-26 Genentech, Inc. Procédés de traitement d'un cancer positif her2
EP4335851A2 (fr) 2015-11-25 2024-03-13 ImmunoGen, Inc. Formulations pharmaceutiques et leurs procédés d'utilisation
WO2017091745A1 (fr) 2015-11-25 2017-06-01 Immunogen, Inc. Formulations pharmaceutiques et leurs procédés d'utilisation
US10227410B2 (en) 2015-12-07 2019-03-12 Xencor, Inc. Heterodimeric antibodies that bind CD3 and PSMA
US11897959B2 (en) 2016-04-15 2024-02-13 Bioatla, Inc. Anti-AXL antibodies, antibody fragments and their immunoconjugates and uses thereof
US11149088B2 (en) 2016-04-15 2021-10-19 Bioatla, Inc. Anti-Axl antibodies, antibody fragments and their immunoconjugates and uses thereof
US11788066B2 (en) 2016-04-26 2023-10-17 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
US11208632B2 (en) 2016-04-26 2021-12-28 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
WO2017194568A1 (fr) 2016-05-11 2017-11-16 Sanofi Schéma de traitement utilisant un anticorps immunoconjugué anti-muc1 à base de maytansinoïde pour le traitement des tumeurs
WO2017197234A1 (fr) 2016-05-13 2017-11-16 Bioatla, Llc Anticorps anti-ror2, fragments d'anticorps, leurs immunoconjugués et utilisations correspondantes
EP4122958A1 (fr) 2016-05-13 2023-01-25 BioAtla, Inc. Anticorps anti-ror2, fragments d'anticorps, leurs immunoconjugués et leurs utilisations
US11254742B2 (en) 2016-05-13 2022-02-22 Bioatla, Inc. Anti-Ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof
US11879011B2 (en) 2016-05-13 2024-01-23 Bioatla, Inc. Anti-ROR2 antibodies, antibody fragments, their immunoconjucates and uses thereof
WO2017205741A1 (fr) 2016-05-27 2017-11-30 Genentech, Inc. Procédé bioanalytique pour la caractérisation de conjugués anticorps-médicament spécifiques d'un site
US10640563B2 (en) 2016-06-08 2020-05-05 Abbvie Inc. Anti-B7-H3 antibodies and antibody drug conjugates
WO2017214322A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
WO2017214456A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
WO2017214339A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
WO2017214458A2 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
US11236170B2 (en) 2016-06-14 2022-02-01 Xencor, Inc. Bispecific checkpoint inhibitor antibodies
US11492407B2 (en) 2016-06-14 2022-11-08 Xencor, Inc. Bispecific checkpoint inhibitor antibodies
US10787518B2 (en) 2016-06-14 2020-09-29 Xencor, Inc. Bispecific checkpoint inhibitor antibodies
WO2018004338A1 (fr) 2016-06-27 2018-01-04 Tagworks Pharmaceuticals B.V. Tétrazine clivable utilisée dans l'activation de médicaments bio-orthogonaux
US10316088B2 (en) 2016-06-28 2019-06-11 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
US11225521B2 (en) 2016-06-28 2022-01-18 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
US12054545B2 (en) 2016-06-28 2024-08-06 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
WO2018045325A1 (fr) 2016-09-02 2018-03-08 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec des duocars
EP4282969A2 (fr) 2016-09-02 2023-11-29 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec des duocars
WO2021102337A1 (fr) 2016-09-02 2021-05-27 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec des duocar
WO2020061194A2 (fr) 2016-09-02 2020-03-26 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec des duocars
US10501543B2 (en) 2016-10-14 2019-12-10 Xencor, Inc. IL15/IL15Rα heterodimeric Fc-fusion proteins
US10550185B2 (en) 2016-10-14 2020-02-04 Xencor, Inc. Bispecific heterodimeric fusion proteins containing IL-15-IL-15Rα Fc-fusion proteins and PD-1 antibody fragments
EP3888691A1 (fr) 2016-11-14 2021-10-06 Hangzhou Dac Biotech Co., Ltd. Lieurs de conjugaison, conjugués médicament-molécule de liaison à une cellule contenant lesdits lieurs, procédés de préparation et d'utilisation de tels conjugués avec les lieurs
WO2018091724A1 (fr) 2016-11-21 2018-05-24 Cureab Gmbh Anticorps anti-gp73 et immunoconjugués
EP4015532A1 (fr) 2016-11-21 2022-06-22 cureab GmbH Anticorps et immunoconjugués anti-gp73
US11964025B2 (en) 2016-11-23 2024-04-23 Mersana Therapeutics, Inc. Peptide-containing linkers for antibody-drug conjugates
WO2018098269A2 (fr) 2016-11-23 2018-05-31 Mersana Therapeutics, Inc. Lieurs contenant des peptides pour des conjugués anticorps-médicament
WO2018098258A2 (fr) 2016-11-23 2018-05-31 Immunogen, Inc. Sulfonation sélective de dérivés de benzodiazépine
US10925971B2 (en) 2016-11-29 2021-02-23 Regeneron Pharmaceuticals, Inc. Methods of treating PRLR positive breast cancer
RU2644280C1 (ru) * 2016-12-12 2018-02-08 Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) Способ получения противоопухолевого коньюгата на основе человеческого сывороточного альбумина, содержащего терапевтические и контрастирующий агенты
WO2018129524A1 (fr) 2017-01-09 2018-07-12 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-mésothéline
EP3882265A1 (fr) 2017-01-09 2021-09-22 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-mésothéline
EP4183798A1 (fr) 2017-01-09 2023-05-24 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-mésothéline
WO2018142322A1 (fr) 2017-02-03 2018-08-09 Novartis Ag Conjugués anticorps-médicament anti-ccr7
WO2018160539A1 (fr) 2017-02-28 2018-09-07 Immunogen, Inc. Dérivés de maytansinoïdes comprenant des lieurs peptidiques auto-immolables et conjugués correspondants
EP4257614A2 (fr) 2017-03-10 2023-10-11 Berlin-Chemie AG Combinaisons pharmaceutiques comprenant un anticorps anti-ly75
US11365258B2 (en) 2017-03-10 2022-06-21 Berlin-Chemie Ag Pharmaceutical combinations comprising an anti-LY75 antibody
WO2018175988A1 (fr) 2017-03-24 2018-09-27 Lentigen Technology, Inc. Compositions et procédés pour le traitement du cancer avec immunothérapie anti-cd33
WO2018185618A1 (fr) 2017-04-03 2018-10-11 Novartis Ag Conjugués de médicament-anticorps anti-cdh6 et combinaisons d'anticorps anti-gitr et méthodes de traitement
WO2018195302A1 (fr) 2017-04-19 2018-10-25 Bluefin Biomedicine, Inc. Anticorps anti-vtcn1 et conjugués anticorps-médicament
WO2018195243A1 (fr) 2017-04-20 2018-10-25 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et leurs conjugués
WO2018237262A1 (fr) 2017-06-22 2018-12-27 Mersana Therapeutics, Inc. Procédés de production de matrices polymères transportant des médicaments, et conjugués protéine-polymère-médicament
US11084863B2 (en) 2017-06-30 2021-08-10 Xencor, Inc. Targeted heterodimeric Fc fusion proteins containing IL-15 IL-15alpha and antigen binding domains
WO2019028051A1 (fr) 2017-07-31 2019-02-07 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd19/cd20
WO2019025983A1 (fr) 2017-08-01 2019-02-07 Medimmune, Llc Conjugué anticorps monoclonal-médicament dirigé contre bcma
WO2019055842A1 (fr) 2017-09-15 2019-03-21 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd19
EP4279086A2 (fr) 2017-09-15 2023-11-22 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd19
WO2019079249A1 (fr) 2017-10-16 2019-04-25 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd22
EP4279584A2 (fr) 2017-10-16 2023-11-22 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd22
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
US11312770B2 (en) 2017-11-08 2022-04-26 Xencor, Inc. Bispecific and monospecific antibodies using novel anti-PD-1 sequences
US11319355B2 (en) 2017-12-19 2022-05-03 Xencor, Inc. Engineered IL-2 Fc fusion proteins
WO2019126464A2 (fr) 2017-12-20 2019-06-27 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du vih/sida par immunothérapie
WO2019133652A1 (fr) 2017-12-28 2019-07-04 Immunogen, Inc. Dérivés de benzodiazépine
WO2019175125A1 (fr) 2018-03-13 2019-09-19 F. Hoffmann-La Roche Ag Polythérapie avec des agonistes de 4-1 bb (cd137) ciblés
US10982006B2 (en) 2018-04-04 2021-04-20 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
US11505595B2 (en) 2018-04-18 2022-11-22 Xencor, Inc. TIM-3 targeted heterodimeric fusion proteins containing IL-15/IL-15RA Fc-fusion proteins and TIM-3 antigen binding domains
US11524991B2 (en) 2018-04-18 2022-12-13 Xencor, Inc. PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof
WO2019212356A1 (fr) 2018-05-04 2019-11-07 Tagworks Pharmaceuticals B .V. Tétrazines pour un rendement élevé de conjugaison de chimie click in vivo et un rendement élevé de libération de chimie click
WO2019212357A1 (fr) 2018-05-04 2019-11-07 Tagworks Pharmaceuticals B.V. Composés comprenant un lieur pour augmenter la stabilité de transcyclooctène
EP4382167A2 (fr) 2018-05-04 2024-06-12 Tagworks Pharmaceuticals B.V. Composés comprenant un lieur pour augmenter la stabilité du transcyclooctène
WO2019238843A1 (fr) 2018-06-14 2019-12-19 Berlin-Chemie Ag Associations pharmaceutiques
WO2020010079A2 (fr) 2018-07-02 2020-01-09 Amgen Inc. Protéine de liaison à l'antigène anti-steap1
US11530274B2 (en) 2018-07-02 2022-12-20 Amgen Inc. Anti-STEAP1 antigen-binding protein
US12006370B2 (en) 2018-07-23 2024-06-11 Heidelberg Pharma Research Gmbh Use of anti-CD5 antibody drug conjugate (ADC) in allogeneic cell therapy
WO2020061498A1 (fr) 2018-09-20 2020-03-26 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer au moyen d'une immunothérapie anti-cd123
US12037403B2 (en) 2018-09-20 2024-07-16 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD123 immunotherapy
WO2020069184A2 (fr) 2018-09-26 2020-04-02 Lentigen Technology, Inc. Compositions et procédés de traitement du cancer par immunothérapie anti-cd19/cd22
US11358999B2 (en) 2018-10-03 2022-06-14 Xencor, Inc. IL-12 heterodimeric Fc-fusion proteins
EP4227320A2 (fr) 2018-10-15 2023-08-16 F. Hoffmann-La Roche AG Méthodes de traitement du cancer du sein résiduel avec la trastuzumab emtansine
WO2020081119A1 (fr) 2018-10-15 2020-04-23 Genentech, Inc. Méthodes de traitement de cancer du sein résiduel à l'aide de trastuzumab emtansine
WO2020092385A1 (fr) 2018-10-29 2020-05-07 Mersana Therapeutics, Inc. Conjugués anticorps-médicament modifiés par une cystéine avec des lieurs contenant des peptides
WO2020113108A1 (fr) 2018-11-30 2020-06-04 Lentigen Technology, Inc. Compositions et méthodes pour le traitement du cancer avec une immunothérapie anti-cd38
US12029792B2 (en) 2018-12-04 2024-07-09 Der-Yang Tien Stereocomplexes for the delivery of anti-cancer agents
WO2020117257A1 (fr) 2018-12-06 2020-06-11 Genentech, Inc. Thérapie combinée de lymphome diffus à grandes cellules b comprenant des immuno-conjugués anti-cd79b, un agent alkylant et un anticorps anti-cd20
US11472890B2 (en) 2019-03-01 2022-10-18 Xencor, Inc. Heterodimeric antibodies that bind ENPP3 and CD3
WO2020181164A1 (fr) 2019-03-06 2020-09-10 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer au moyen de récepteurs antigéniques chimériques automoteurs
WO2020191342A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps anti-claudine-6 et conjugués de médicaments
WO2020191344A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps de claudin-6 bispécifiques
WO2020205564A1 (fr) 2019-03-29 2020-10-08 Immunogen, Inc. Dérivés de bis-benzodiazépine cytotoxiques et leurs conjugués avec des agents de liaison à une cellule pour inhiber la croissance cellulaire anormale ou pour traiter des maladies prolifératives
WO2020216947A1 (fr) 2019-04-24 2020-10-29 Heidelberg Pharma Research Gmbh Conjugués anticorps-médicaments d'amatoxine et leurs utilisations
EP4316524A2 (fr) 2019-04-26 2024-02-07 ImmunoGen, Inc. Derives de camptothecine
WO2020219287A1 (fr) 2019-04-26 2020-10-29 Immunogen, Inc. Dérivés de camptothécine
WO2020232169A1 (fr) 2019-05-14 2020-11-19 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome folliculaire
US11052112B2 (en) 2019-05-30 2021-07-06 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-BCMA immunotherapy
WO2020243546A1 (fr) 2019-05-30 2020-12-03 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-bcma
WO2020256546A1 (fr) 2019-06-17 2020-12-24 Tagworks Pharmaceuticals B.V. Composés pour libération de chimie click rapide et efficace
EP4382129A2 (fr) 2019-06-17 2024-06-12 Tagworks Pharmaceuticals B.V. Composés pour libération de clic rapide et efficace
WO2020256544A1 (fr) 2019-06-17 2020-12-24 Tagworks Pharmaceuticals B.V. Tétrazines pour une vitesse et un rendement de libération de chimie clic élevés
WO2021003297A1 (fr) 2019-07-02 2021-01-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps monoclonaux se liant à egfrviii et leurs utilisations
WO2021076196A1 (fr) 2019-10-18 2021-04-22 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
WO2021097220A1 (fr) 2019-11-15 2021-05-20 Seagen Inc. Méthodes de traitement du cancer du sein her2 positif avec du tucatinib en combinaison avec un conjugué médicament-anticorps anti-her2
US11453711B2 (en) 2019-12-31 2022-09-27 Beijing Ql Biopharmaceutical Co., Ltd. Fusion proteins of GLP-1 and GDF15 and conjugates thereof
US11786605B2 (en) 2020-01-09 2023-10-17 Mersana Therapeutics, Inc. Site specific antibody-drug conjugates with peptide-containing linkers
WO2021142199A1 (fr) 2020-01-09 2021-07-15 Mersana Therapeutics, Inc. Conjugués anticorps-médicament spécifiques à un site avec des lieurs contenant des peptides
US11510990B2 (en) 2020-01-11 2022-11-29 Beijing Ql Biopharmaceutical Co., Ltd. Conjugates of fusion proteins of GLP-1 and FGF21
WO2021173773A1 (fr) 2020-02-25 2021-09-02 Mediboston, Inc. Dérivés de camptothécine et leurs utilisations
WO2021217051A1 (fr) 2020-04-24 2021-10-28 Genentech, Inc. Procédés d'utilisation d'immunoconjugués anti-cd79b
WO2021220199A1 (fr) 2020-04-30 2021-11-04 Novartis Ag Conjugués anticorps-médicament ccr7 pour le traitement du cancer
US11919956B2 (en) 2020-05-14 2024-03-05 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3
WO2021262723A1 (fr) 2020-06-22 2021-12-30 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie tslpr-cd19 ou tslpr-cd22
WO2022010797A2 (fr) 2020-07-07 2022-01-13 Bionecure Therapeutics, Inc. Nouveaux maytansinoïdes en tant que charges utiles d'adc et leur utilisation pour le traitement du cancer
US11529394B2 (en) 2020-09-30 2022-12-20 Beijing Ql Biopharmaceutical Co., Ltd. Polypeptide conjugates and methods of uses
WO2022099026A1 (fr) 2020-11-05 2022-05-12 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd19/cd22
US11759527B2 (en) 2021-01-20 2023-09-19 Abbvie Inc. Anti-EGFR antibody-drug conjugates
WO2022180581A2 (fr) 2021-02-25 2022-09-01 Mediboston Limited Conjugués anticorps anti-her2-médicament et leurs utilisations
US11739144B2 (en) 2021-03-09 2023-08-29 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CLDN6
US11859012B2 (en) 2021-03-10 2024-01-02 Xencor, Inc. Heterodimeric antibodies that bind CD3 and GPC3
WO2022241446A1 (fr) 2021-05-12 2022-11-17 Genentech, Inc. Méthodes d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
WO2023019092A1 (fr) 2021-08-07 2023-02-16 Genentech, Inc. Méthodes d'utilisation d'immunoconjugués anti-cd79b pour traiter un lymphome diffus à grandes cellules b
WO2023031445A2 (fr) 2021-09-06 2023-03-09 Veraxa Biotech Gmbh Nouveaux variants d'aminoacyl-arnt synthétase pour l'expansion de code génétique dans des eucaryotes
WO2023089314A1 (fr) 2021-11-18 2023-05-25 Oxford Biotherapeutics Limited Combinaisons pharmaceutiques
EP4186529A1 (fr) 2021-11-25 2023-05-31 Veraxa Biotech GmbH Conjugués anticorps-charge utile améliorés (apcs) préparés par conjugaison spécifique à un site à l'aide d'une expansion de code génétique
WO2023094525A1 (fr) 2021-11-25 2023-06-01 Veraxa Biotech Gmbh Conjugués anticorps-charge utile améliorés (apc) préparés par conjugaison spécifique à un site à l'aide d'une expansion de code génétique
WO2023104941A1 (fr) 2021-12-08 2023-06-15 European Molecular Biology Laboratory Charges utiles hydrophiles fonctionnalisées à la tétrazine destinées à la préparation de conjugués de ciblage
WO2023105248A1 (fr) 2021-12-11 2023-06-15 Cancer Research Technology Limited Immunothérapie pour le cancer
WO2023158305A1 (fr) 2022-02-15 2023-08-24 Tagworks Pharmaceuticals B.V. Protéine il12 masquée
EP4372000A2 (fr) 2022-02-15 2024-05-22 Tagworks Pharmaceuticals B.V. Proteine il12 masquee
WO2023168243A1 (fr) 2022-03-02 2023-09-07 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd123
US11590169B1 (en) 2022-03-02 2023-02-28 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD123 immunotherapy
WO2023169896A1 (fr) 2022-03-09 2023-09-14 Astrazeneca Ab MOLÉCULES DE LIAISON DIRIGÉES CONTRE LE FRα
WO2023170216A1 (fr) 2022-03-11 2023-09-14 Astrazeneca Ab PROCÉDÉ DE NOTATION D'UNE THÉRAPIE PAR CONJUGUÉ ANTICORPS-MÉDICAMENTS ANTI-FRα
US12129309B2 (en) 2022-05-04 2024-10-29 Xencor, Inc. Heterodimeric antibodies that bind CD3 and CD38
WO2024013724A1 (fr) 2022-07-15 2024-01-18 Pheon Therapeutics Ltd Conjugués anticorps-médicament
WO2024023735A1 (fr) 2022-07-27 2024-02-01 Mediboston Limited Dérivés d'auristatine et conjugués de ceux-ci
WO2024026107A2 (fr) 2022-07-28 2024-02-01 Lentigen Technology, Inc. Thérapies par récepteur antigénique chimérique pour le traitement de tumeurs solides
WO2024044743A1 (fr) 2022-08-26 2024-02-29 Lentigen Technology, Inc. Compositions et méthodes de traitement du cancer par immunothérapie anti-cd20/cd19 entièrement humaine
WO2024080872A1 (fr) 2022-10-12 2024-04-18 Tagworks Pharmaceuticals B.V. Bicyclononènes contraints
WO2024121632A1 (fr) 2022-12-09 2024-06-13 Crispr Therapeutics Ag Utilisation d'un conjugué anticorps-médicament (adc) anti-cd117
WO2024153789A1 (fr) 2023-01-20 2024-07-25 Basf Se Composition de biopolymère stabilisée, sa fabrication et son utilisation
WO2024170660A1 (fr) 2023-02-16 2024-08-22 Astrazeneca Ab Polythérapies pour le traitement du cancer avec des molécules de liaison thérapeutiques
WO2024191293A1 (fr) 2023-03-10 2024-09-19 Tagworks Pharmaceuticals B.V. Trans-cyclooctène à lieur t amélioré

Also Published As

Publication number Publication date
AU2002251880B2 (en) 2005-05-19
EP1390370A1 (fr) 2004-02-25
WO2002098883A1 (fr) 2002-12-12
DK2348024T3 (en) 2015-11-02
JP5271302B2 (ja) 2013-08-21
NZ523655A (en) 2005-05-27
DK1390370T3 (en) 2016-08-01
EP2348024B1 (fr) 2015-07-29
US20030055226A1 (en) 2003-03-20
CA2417858A1 (fr) 2002-12-12
JP5190170B2 (ja) 2013-04-24
CY1116855T1 (el) 2017-04-05
EP1390370A4 (fr) 2005-07-06
PT1390370E (pt) 2016-06-09
ES2574640T3 (es) 2016-06-21
HK1060355A1 (zh) 2004-08-06
US7368565B2 (en) 2008-05-06
CY1117729T1 (el) 2017-05-17
EP2348024A2 (fr) 2011-07-27
HK1149765A1 (en) 2011-10-14
CA2417858C (fr) 2011-07-12
JP2010155863A (ja) 2010-07-15
EP1390370B1 (fr) 2016-04-13
JP2004520450A (ja) 2004-07-08
EP2348024A3 (fr) 2012-04-18
PT2348024E (pt) 2015-11-13
ES2551233T3 (es) 2015-11-17

Similar Documents

Publication Publication Date Title
US6441163B1 (en) Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
AU2002251880A1 (en) Method for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
EP3031810B1 (fr) Conjugués de maytansinoïde-agent de liaison de cellule
US20180043013A1 (en) Cytotoxic agents comprising new maytansinoids (dm4)
US6333410B1 (en) Process for the preparation and purification of thiol-containing maytansinoids
US5416064A (en) Cytotoxic agents comprising maytansinoids and their therapeutic use
EP0425235B1 (fr) Agents cytotoxiques contenant des maytansinoides et leur application thérapeutique

Legal Events

Date Code Title Description
AS Assignment

Owner name: IMMUNOGEN, INC., MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CHARI, RAVI V.J.;WIDDISON, WAYNE C.;REEL/FRAME:012210/0589

Effective date: 20010820

STCF Information on status: patent grant

Free format text: PATENTED CASE

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

AS Assignment

Owner name: IMMUNOGEN, INC., MASSACHUSETTS

Free format text: ADDRESS CHANGE;ASSIGNOR:IMMUNOGEN, INC.;REEL/FRAME:020930/0905

Effective date: 20080324

Owner name: IMMUNOGEN, INC.,MASSACHUSETTS

Free format text: ADDRESS CHANGE;ASSIGNOR:IMMUNOGEN, INC.;REEL/FRAME:020930/0905

Effective date: 20080324

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12